Change search
Refine search result
3456789 251 - 300 of 1574
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 251.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bylock, Anders
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischemic events: Observations from the ESTEEM trial2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 6, p. 692-698Article in journal (Refereed)
    Abstract [en]

    AIM: Patients with a recent myocardial infarction have an increased risk of recurrent ischaemic events. In the ESTEEM trial, the oral direct thrombin inhibitor ximelagatran reduced the risk of new ischaemic events when compared with placebo in aspirin treated post myocardial infarction patients. Ximelagatran persistently reduced markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer levels. The aim of this substudy was to evaluate the levels of these markers and activated thromboplastin time (APTT) in relation to new ischaemic events or bleeding. METHODS AND RESULTS: In the substudy, 518 out of 1883 patients were included and within 14 days after a myocardial infarction randomized to ximelagatran or placebo for 6 months. The clinical endpoints death, myocardial infarction, severe recurrent ischaemia, ischaemic stroke, and bleeding were evaluated. The levels of F1 + 2, D-dimer, and APTT were analysed at randomization and in serial samples during the study. Ximelagatran treatment appeared to have a larger treatment effect in patients with F1 + 2 and D-dimer levels above the median at randomization with a reduction of ischaemic events from 18 to 9% (P = 0.03) for F1 + 2 and from 20 to 9% for D-dimer (P = 0.009). A reduction of D-dimer levels was found in 60% of the patients 1 week after randomization and these patients had less ischaemic events when compared with patients with unchanged or increased levels (P = 0.03) regardless of treatment. F1 + 2 and D-dimer levels were unrelated to bleeding risk. In the ximelagatran group, increased APTT was not related to ischaemic events but associated with a raised risk of bleeding. CONCLUSION: A reduction of initially high coagulation activity, as measured by the D-dimer level, in patients with recent myocardial infarction identifies patients with a decreased risk of new ischaemic events, regardless whether the reduction occurs spontaneously or is induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.

  • 252.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Treatment with an Oral Direct Thrombin Inhibitor Decreases Platelet Activity but Increases Markers of Inflammation in Patients with Myocardial Infarction.2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 215-223Article in journal (Refereed)
    Abstract [en]

    Background: Thrombin has a role not only in the coagulation process but also in inflammatory responses. Oral direct thrombin inhibitors (DTIs) are currently being evaluated in patients with thromboembolic diseases. Objectives:  To investigate whether an oral DTI affects markers for platelet and inflammatory activity after myocardial infarction (MI). Methods:  A total of 518 patients with MI were randomly assigned to ximelagatran treatment (four different dose groups) in combination with aspirin, or aspirin alone for 6 months. The levels of soluble (s) P-selectin, soluble tissue factor, C-reactive protein (CRP), interleukin (IL)-10 and IL-18 were analysed in serial blood samples.

    Results: sP-selectin concentration increased after 1 week and persisted at an elevated level for 6 months in all study groups (p<0.001). In the two highest ximelagatran dose groups, there was a reduced increase in sP-selectin compared to treatment with lower doses of ximelagatran and aspirin alone (p=0.01 and p=0.002, respectively). IL-18 levels did not change in the aspirin alone treatment group. By contrast, there was an elevation in IL-18 level in the lower and higher ximelagatran dose groups after 6 months (p=0.006 and p<0.001, respectively). Ximelagatran increased IL-10 levels (p=0.002) and reduced the decrease in CRP levels after 6 months compared to treatment with aspirin alone (p=0.002).

    Conclusion: A persistent elevation of platelet activity is found in patients with a recent MI after the cessation of acute antithrombotic treatment, and the addition of an oral DTI at higher doses decreases the activity. By contrast, long-term treatment with a DTI increases the levels of several markers of inflammation. Further studies with prolonged exposure of oral DTIs are needed for evaluation of the effect on inflammatory processes and to determine whether these agents influence clinical outcomes.

  • 253.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Schollin, M.
    Alexander, J. H.
    Bersh, B. J.
    Horowitz, J.
    Hylek, E. M.
    Mohan, P.
    Granger, C. B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Increased levels of D-dimer in atrial fibrillation identify patients with higher risk of thromboembolic events and death2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 969-969Article in journal (Other academic)
  • 254.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, J. H.
    Ansell, J.
    De Caterina, R.
    Gersh, B. J.
    Granger, C. B.
    Hanna, M.
    Horowitz, J. D.
    Huber, K.
    Husted, S.
    Hylek, E. M.
    Lopes, R. D.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation: observations from the ARISTOTLE trial2014In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 12, no 9, p. 1401-1412Article in journal (Refereed)
    Abstract [en]

    BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at randomization. ResultsHigher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR][Q4 vs. Q1]1.72, 95% confidence interval [CI]1.14-2.59, P=0.003), death (HR[Q4 vs. Q1]4.04, 95%CI3.06-5.33) and major bleeding (HR[Q4 vs. Q1]2.47, 95%CI1.77-3.45, P<0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS(2) score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. ConclusionIn anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.

  • 255.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H
    Alings, Marco
    De Caterina, Raffaele
    Gersh, Bernard J
    Granger, Christopher B
    Halvorsen, Sigrun
    Hanna, Michael
    Huber, Kurt
    Hylek, Elaine M
    Lopes, Renato D
    Oh, Byung-Hee
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.2019In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 3, p. 235-242Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).

    METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.

    RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.

    CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.

    TRIAL REGISTRATION NUMBER: NCT00412984.

  • 256.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersson, Ulrika
    Hylek, E. M.
    Husted, S.
    De Caterina, R.
    Hanna, M.
    Lopes, R. D.
    Granger, C. B.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    The efficacy of apixaban compared to warfarin in patients with atrial fibrillation with high coagulation activity despite anticoagulant treatment2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 866-867Article in journal (Refereed)
  • 257. Chung, Sheng-Chia
    et al.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nicholas, Owen
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jeppsson, Anders
    Wolfe, Charles
    Heuschmann, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deanfield, John
    Timmis, Adam
    Jernberg, Tomas
    Hemingway, Harry
    Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK2014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 383, no 9925, p. 1305-1312Article in journal (Refereed)
    Abstract [en]

    Background International research for acute myocardial infarction lacks comparisons of whole health systems. We assessed time trends for care and outcomes in Sweden and the UK. Methods We used data from national registries on consecutive patients registered between 2004 and 2010 in all hospitals providing care for acute coronary syndrome in Sweden and the UK. The primary outcome was all-cause mortality 30 days after admission. We compared effectiveness of treatment by indirect casemix standardisation. This study is registered with ClinicalTrials.gov, number NCT01359033. Findings We assessed data for 119 786 patients in Sweden and 391 077 in the UK. 30-day mortality was 7.6% (95% CI 7.4-7.7) in Sweden and 10.5% (10.4-10.6) in the UK. Mortality was higher in the UK in clinically relevant subgroups defined by troponin concentration, ST-segment elevation, age, sex, heart rate, systolic blood pressure, diabetes mellitus status, and smoking status. In Sweden, compared with the UK, there was earlier and more extensive uptake of primary percutaneous coronary intervention (59% vs 22%) and more frequent use of beta blockers at discharge (89% vs 78%). After casemix standardisation the 30-day mortality ratio for UK versus Sweden was 1.37 (95% CI 1.30-1.45), which corresponds to 11 263 (95% CI 9620-12 827) excess deaths, but did decline over time (from 1.47, 95% CI 1.38-1.58 in 2004 to 1.20, 1.12-1.29 in 2010; p=0.01). Interpretation We found clinically important differences between countries in acute myocardial infarction care and outcomes. International comparisons research might help to improve health systems and prevent deaths.

  • 258. Chung, Sheng-Chia
    et al.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gale, Chris P.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Deanfield, John
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Timmis, Adam
    Jernberg, Tomas
    Hemingway, Harry
    Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h3913Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. DESIGN Population based longitudinal cohort study using nationwide clinical registries. SETTING AND PARTICIPANTS Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119 786 patients) and the UK (NICOR/MINAP, n=242; 391 077 patients), 2004-10. MAIN OUTCOME MEASURES Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. RESULTS Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% v 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% v 6.6% in Sweden; 12.7% v 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals' use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. CONCLUSION Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction.

  • 259.
    Chung, Sheng-Chia
    et al.
    UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.;UCL, Inst Hlth Informat, London NW1 2DA, England..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Gale, Chris P.
    Univ Leeds, Cardiovasc Hlth Sci, Leeds, W Yorkshire, England..
    Timmis, Adam
    Barts Hlth London, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Jernberg, Tomas
    Karolinska Inst, Dept Med, Sect Cardiol, Stockholm, Sweden..
    Hemingway, Harry
    UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.;UCL, Inst Hlth Informat, London NW1 2DA, England..
    Hospital Variation in AMI Outcome in UK and Sweden: Authors’ reply to Gupta2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h5140Article in journal (Refereed)
  • 260.
    Collinson, Paul
    et al.
    St George Hosp, Dept Clin Blood Sci, London SW17 0RE, England.;St George Hosp, Dept Cardiol, London SW17 0RE, England.;Sch Med, London, England..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Type 2 myocardial infarction: the chimaera of cardiology?2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 21, p. 1697-1703Article, review/survey (Refereed)
    Abstract [en]

    The term type 2 myocardial infarction first appeared as part of the universal definition of myocardial infarction. It was introduced to cover a group of patients who had elevation of cardiac troponin but did not meet the traditional criteria for acute myocardial infarction although they were considered to have an underlying ischaemic aetiology for the myocardial damage observed. Since first inception, the term type 2 myocardial infarction has always been vague. Although attempts have been made to produce a systematic definition of what constitutes a type 2 myocardial infarction, it has been more often characterised by what it is not rather than what it is. Clinical studies that have used type 2 myocardial infarction as a diagnostic criterion have produced disparate incidence figures. The range of associated clinical conditions differs from study to study. Additionally, there are no agreed or evidence-based treatment strategies for type 2 myocardial infarction. The authors believe that the term type 2 myocardial infarction is confusing and not evidence-based. They consider that there is good reason to stop using this term and consider instead the concept of secondary myocardial injury that relates to the underlying pathophysiology of the primary clinical condition.

  • 261. Connolly, Stuart J.
    et al.
    Ezekowitz, Michael D.
    Yusuf, Salim
    Eikelboom, John
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Parekh, Amit
    Pogue, Janice
    Reilly, Paul A.
    Themeles, Ellison
    Varrone, Jeanne
    Wang, Susan
    Alings, Marco
    Xavier, Denis
    Zhu, Jun
    Diaz, Rafael
    Lewis, Basil S.
    Darius, Harald
    Diener, Hans-Christoph
    Joyner, Campbell D.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dabigatran versus warfarin in patients with atrial fibrillation2009In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 361, no 12, p. 1139-1151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. RESULTS: Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). CONCLUSIONS: In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)

  • 262. Connolly, Stuart J.
    et al.
    Ezekowitz, Michael D.
    Yusuf, Salim
    Reilly, Paul A.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Newly Identified Events in the RE-LY Trial2010In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 363, no 19, p. 1875-1876Article in journal (Refereed)
  • 263. Connolly, Stuart J.
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ezekowitz, Michael D.
    Eikelboom, John
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Reilly, Paul A.
    Brueckmann, Martina
    Pogue, Janice
    Alings, Marco
    Amerena, John V.
    Avezum, Alvaro
    Baumgartner, Iris
    Budaj, Andrzej J.
    Chen, Jyh-Hong
    Dans, Antonio L.
    Darius, Harald
    Di Pasquale, Giuseppe
    Ferreira, Jorge
    Flaker, Greg C.
    Flather, Marcus D.
    Franzosi, Maria Grazia
    Golitsyn, Sergey P.
    Halon, David A.
    Heidbuchel, Hein
    Hohnloser, Stefan H.
    Huber, Kurt
    Jansky, Petr
    Kamensky, Gabriel
    Keltai, Matyas
    Kim, Sung Soon
    Lau, Chu-Pak
    Le Heuzey, Jean-Yves
    Lewis, Basil S.
    Liu, Lisheng
    Nanas, John
    Omar, Razali
    Pais, Prem
    Pedersen, Knud E.
    Piegas, Leopoldo S.
    Raev, Dimitar
    Smith, Pal J.
    Talajic, Mario
    Tan, Ru San
    Tanomsup, Supachai
    Toivonen, Lauri
    Vinereanu, Dragos
    Xavier, Denis
    Zhu, Jun
    Wang, Susan Q.
    Duffy, Christine O.
    Themeles, Ellison
    Yusuf, Salim
    The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 3, p. 237-243Article in journal (Refereed)
    Abstract [en]

    Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. 

  • 264. Connolly, Stuart J.
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yusuf, Salim
    Additional Events in the RE-LY Trial2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, no 15, p. 1464-1465Article in journal (Refereed)
  • 265. Cornel, J.
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, R. D.
    Mohan, P.
    Neely, M.
    Amerena, J.
    Huo, Y.
    Alexander, J. H.
    Harrington, R. A.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Apixaban after acute coronary syndrome in patients with heart failure: insights from the APPRAISE-2 trial2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 335-336Article in journal (Other academic)
  • 266. Cornel, Jan H.
    et al.
    Becker, Richard C.
    Goodman, Shaun G.
    Husted, Steen
    Katus, Hugo
    Santoso, Anwar
    Steg, Gabriel
    Storey, Robert F.
    Vintila, Marius
    Sun, Jie L.
    Horrow, Jay
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Harrington, Robert
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 164, no 3, p. 334-342Article in journal (Refereed)
    Abstract [en]

    Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.

    Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.

    Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).

    Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.

  • 267. Cornel, Jan H.
    et al.
    Lopes, Renato D.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stevens, Susanna R.
    Neely, Megan L.
    Liaw, Danny
    Miller, Julie
    Mohan, Puneet
    Amerena, John
    Raev, Dimitar
    Huo, Yong
    Urina-Triana, Miguel
    Cazorla, Alex Gallegos
    Vinereanu, Dragos
    Fridrich, Viliam
    Harrington, Robert A.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Alexander, John H.
    Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 4, p. 531-538Article in journal (Refereed)
    Abstract [en]

    Background Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. Methods High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Results Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. Conclusions In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.

  • 268. Cornel, Jan H.
    et al.
    Tricoci, Pierluigi
    Lokhnygina, Yuliya
    Moliterno, David J.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Aylward, Philip E.
    Clare, Robert M.
    Chen, Edmond
    Leonardi, Sergio
    de Werf, Frans Van
    White, Harvey D.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Strony, John
    Mahaffey, Kenneth W.
    Harrington, Robert A.
    Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes (from the TRACER Trial)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 10, p. 1325-1332Article in journal (Refereed)
    Abstract [en]

    We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIn/IIIa group; adjusted FIR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

  • 269. Cornelis, M C
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, J
    Elmståhl, S
    Söderberg, S
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Targeted proteomic analysis of habitual coffee consumption.2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

    OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).

    METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

    RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10(-7) ), but not in ULSAM (β, -0.034, P = 0.16).

    CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

  • 270.
    Costa, Francesco
    et al.
    Univ Messina, Dept Clin & Expt Med, Policlin G Martino, Messina, Italy;Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Van Klaveren, David
    Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands;Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA.
    Feres, Fausto
    Ist Dante Pazzanese Cardiol, Sao Paulo, Brazil.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Raber, Lorenz
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Pilgrim, Thomas
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Hong, Myeong-Ki
    Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Seoul, South Korea;Yonsei Univ, Severance Biomed Sci Inst, Coll Med, Seoul, South Korea.
    Kim, Hyo-Soo
    Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea.
    Colombo, Antonio
    Ist Sci San Raffaele, Intervent Cardiol Unit, Milan, Italy;EMO GVM Ctr Cuore Columbus, Intervent Cardiol Unit, Milan, Italy.
    Steg, Philippe Gabriel
    AP HP, FACT, Paris, France;Univ Paris Diderot, Bichat Hosp, Paris, France.
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA;Cardiovasc Res Fdn, New York, NY USA.
    Windecker, Stephan
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Steyerberg, Ewout W.
    Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands.
    Valgimigli, Marco
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, no 7, p. 741-754Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short-or long-term DAPT should be prioritized.

    OBJECTIVES

    This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.

    METHODS

    Complex PCI was defined as $ 3 stents implanted and/or $ 3 lesions treated, bifurcation stenting and/or stent length > 60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high ($ 25) or nonhigh (< 25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.

    RESULTS

    Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference:-3.86%; 95% confidence interval:-7.71 to thorn0.06) and noncomplex PCI strata (absolute risk difference:-1.14%; 95% confidence interval:-2.26 to-0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.

    CONCLUSIONS

    Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.

  • 271.
    Costa, Francesco
    et al.
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.;Erasmus Univ, Med Ctr, Rotterdam, Netherlands.;Univ Messina, Policlin G Martino, Dept Clin & Expt Med, Messina, Italy..
    van Klaveren, David
    Erasmus Univ, Med Ctr, Rotterdam, Netherlands.;Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Heg, Dik
    Univ Bern, Inst Social & Prevent Med, Bern, Switzerland..
    Raber, Lorenz
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Feres, Fausto
    Ist Dante Pazzanese Cardiol, Sao Paulo, Brazil..
    Pilgrim, Thomas
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Hong, Myeong-Ki
    Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Seoul, South Korea.;Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea..
    Kim, Hyo-Soo
    Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea..
    Colombo, Antonio
    EMO GVM Ctr Cuore Columbus, Milan, Italy.;Ist Sci San Raffaele, Intervent Cardiol Dept, Milan, Italy..
    Steg, Philippe Gabriel
    Hop Xavier Bichat, AP HP, Dept Cardiol, Paris, France..
    Zanchin, Thomas
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Palmerini, Tullio
    Univ Bologna, Dipartimento Cardiotoracovasc, Bologna, Italy..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA.;Cardiovasc Res Fdn, New York, NY USA..
    Windecker, Stephan
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Steyerberg, Ewout W.
    Erasmus Univ, Med Ctr, Rotterdam, Netherlands..
    Valgimigli, Marco
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.;Erasmus Univ, Med Ctr, Rotterdam, Netherlands..
    Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 389, no 10073, p. 1025-1034Article in journal (Refereed)
    Abstract [en]

    Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y(12) inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.

    Methods: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk.

    Findings: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0.73 (95% CI 0.61-0.85) in the derivation cohort, and 0.70 (0.65-0.74) in the PLATO trial validation cohort and 0.66 (0.61-0.71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score >= 25), but not in those with lower risk profiles (p(interaction)=0.007), and exerted a significant ischaemic benefit only in this latter group.

    Interpretation: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration.

  • 272.
    Cowper, Patricia A.
    et al.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Sheng, Shubin
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Anstrom, Kevin J.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Stafford, Judith A.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Davidson-Ray, Linda
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Al-Khatib, Sana M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Ansell, Jack
    Hofstra Northwell Sch Med, Dept Med, Hemstead, NY USA..
    Dorian, Paul
    Univ Toronto, Div Cardiol, Toronto, ON, Canada..
    Husted, Steen
    Aarhus Univ, Aarhus, Denmark..
    McMurray, John J. V.
    Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, Glasgow, Lanark, Scotland..
    Steg, P. Gabriel
    Univ Paris Diderot, Dept Hosp Univ Fibrosis Inflammat Remodeling, AP HP, Sorbonne Paris Cite,French Alliance Cardiovasc Cl, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, INSERM, U 1148, Paris, France.;Imperial Coll, Royal Brompton Hosp, Natl Heart & Lung Inst, London, England..
    Alexander, John H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Mark, Daniel B.
    Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA..
    Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial2017In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 2, no 5, p. 525-534Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial.

    OBJECTIVE To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system.

    DESIGN, SETTING, AND PARTICIPANTS This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011.

    INTERVENTIONS Apixaban therapy vs warfarin therapy.

    MAIN OUTCOMES AND MEASURES Within-trial resource use and costwere compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed.

    RESULTS Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$ 60; 95% CI, -$ 2728 to $ 2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($ 53 925 per quality-adjusted life year, with 98% likelihood of meeting a $ 100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon.

    CONCLUSIONS AND RELEVANCE Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness.

  • 273.
    Cunningham, Janet L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Berglund, Lars
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Agreement between physicians' and patients' ratings on the Montgomery-Asberg Depression Rating Scale2011In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 135, no 1-3, p. 148-153Article in journal (Refereed)
    Abstract [en]

    Background: Self-rating scales developed for monitoring depression severity are potentially informative and cost effective tools. There is an increasing tendency to use the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating version (MADRS-S) interchangeably.

    Methods: 400 patients with major depressive disorder were included. Concordance between patient and physician ratings was measured by means of repeated MADRS and MADRS-S ratings during a six-month drug trial and one-year follow-up.

    Results: Overall scores from patients and physicians show the same trends and both are sensitive to improvements. Our results, however, show only moderate to good agreement between patient and physician ratings. Intraclass coefficients ranged from 0.47 to 0.75 with highest agreement at week 8.

    Limitations: Generalizability is restricted to outpatients in general practice with moderate to severe depression. MADRS-S and MADRS scale definitions are similar but not identical concerning language and are scaled differently, 0-6 vs. 0-3, respectively, which may have influenced the results. The exclusion criteria restricted the range of values for the item Suicidal thoughts/Zest for life, which may have reduced the correlations.

    Conclusions: MADRS-S is a suitable tool for following patients' symptoms on a regular basis over time and may also be used to compensate for bias in physicians' ratings in drug trials.

  • 274.
    Cunningham, Janet L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Predicting disagreement between physicians and patients on depression response and remission2013In: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 28, no 3, p. 134-140Article in journal (Refereed)
    Abstract [en]

    Demographic, personality, and disease-related factors all contribute when patients disagree with physicians on the severity of subjective symptoms. This study aims to create a model, on the basis of patient factors at treatment initiation, for longitudinal prediction of disagreement on treatment response and remission in depressed patients. Four hundred patients with major depressive disorder were studied during a clinical drug trial. Repeated assessments with the Montgomery-Asberg Depression Rating Scale (MADRS) and the self-rating version (MADRS-S) were used to indicate response or remission. Factors at baseline and week 2 were tested for inclusion in a model for the prediction of discordance on remission and response between patients and physicians at week 8. The models were then tested, in the same population, at weeks 12, 16, and 24. Model AUCs ranged from 0.71 to 0.74 for week 8. The models that were validated at weeks 12, 16, and 24 indicated stability in the predictive value of the models. The risk for longitudinal disagreement in the evaluation of depression treatment response and remission in clinical practice and drug trials can be predicted using factors at study initiation and at week 2.

  • 275.
    Dagenais, Gilles R.
    et al.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Jung, Hyejung
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Lonn, Eva
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bogaty, Peter M.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Dehghan, Mahshid
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Avezum, Alvaro
    Univ Santo Amaro, Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Jansky, Petr
    Univ Hosp Motol, Prague, Czech Republic.
    Keltai, Matyas
    Semmelweis Univ, Budapest, Hungary.
    Leiter, Lawrence A.
    Univ Toronto, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada;Univ Toronto, Dept Med, Toronto, ON, Canada;Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
    Lopez-Jaramillo, Patricio
    Univ Santander UDES, Med Sch, Res Dept, FOSCAL, Bucaramanga, Colombia.
    Toff, William D.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Bosch, Jackie
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 15, article id e008918Article in journal (Refereed)
    Abstract [en]

    Background-It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. Methods and Results-In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with >= 2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with >= 2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (>= 2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). Conclusions-Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles.

  • 276. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Lambe, Mats
    Bjorkholm, Magnus
    Sandin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sjalander, Anders
    Richter, Johan
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia. Data from Swedish Population-Based Registries2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 277.
    Dahlgren, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Variants of the TCF7L2 gene are associated with beta cell dysfunction and confer an increased risk of type 2 diabetes mellitus in the ULSAM cohort of Swedish elderly men2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 9, p. 1852-1857Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis:

    In a population-based cohort of elderly men with well-defined phenotypes and biochemical markers related to type 2 diabetes mellitus, we analysed two single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, in the transcription factor 7-like 2 gene (TCF7L2), which are associated with an increased risk of type 2 diabetes mellitus.

    Materials and methods:

    The 1,142 subjects were from the population-based Uppsala Longitudinal Study of Adult Men cohort study (see http://www.pubcare.uu.se/ULSAM/ , last accessed in May 2007). Insulin sensitivity was assessed using a euglycaemic-hyperinsulinaemic clamp; fasting intact and 32-33 split proinsulin, immunoreactive insulin and specific insulin were measured in plasma samples. The SNPs rs7903146 and rs12255372 were genotyped using a fluorescent homogeneous single base extension assay. The SNP genotypes were analysed against diabetes prevalence at age 70 using logistic regression and against quantitative biochemical measures using linear regression analysis.

    Results:

    We replicated the association with type 2 diabetes mellitus for both SNPs in this cohort of elderly males. The highest significant odds ratio (2.15, 95% CI 1.20-3.85) was found for SNP rs7903146. The odds ratio for SNP rs12255372 was 1.69 (95% CI 1.20-2.39). Both TCF7L2 SNPs were found to be significantly associated with plasma proinsulin when adjusting for insulin sensitivity, both in the whole cohort and when the diabetic subjects were excluded. Analysis for fasting plasma insulin or insulin sensitivity did not give significant results.

    Conclusions/interpretation:

    The association between the risk alleles of the two SNPs studied and levels of proinsulin in plasma, identified when adjusting for insulin sensitivity using euglycaemic-hyperinsulinaemic clamp measurements in this study, is an important novel finding.

  • 278. Dal-Ré, Rafael
    et al.
    Avendaño-Solà, Cristina
    Bloechl-Daum, Brigitte
    de Boer, Anthonius
    Eriksson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Fuhr, Uwe
    Holm, Søren
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mentz, Robert J
    Perucca, Emilio
    Rosendaal, Frits R
    Treweek, Shaun
    Low risk pragmatic trials do not always require participants' informed consent2019In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 364, article id l1092Article in journal (Other academic)
  • 279. Damman, Peter
    et al.
    Clayton, Tim
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fox, Keith A A
    Hirsch, Alexander
    Windhausen, Fons
    Swahn, Eva
    Pocock, Stuart J
    Tijssen, Jan G P
    de Winter, Robbert J
    Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes: a collaborative analysis of individual data from the FRISC II - ICTUS - RITA-3 (FIR) trials2012In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 98, no 3, p. 207-213Article in journal (Refereed)
    Abstract [en]

    Objective

    To perform a patient-pooled analysis of a routine invasive versus a selective invasive strategy in elderly patients with non-ST segment elevation acute coronary syndrome.

    Methods

    A meta-analysis was performed of patient-pooled data from the FRISC II-ICTUS-RITA-3 (FIR) studies. (Un)adjusted HRs were calculated by Cox regression, with adjustments for variables associated with age and outcomes. The main outcome was 5-year cardiovascular death or myocardial infarction (MI) following routine invasive versus selective invasive management.

    Results

    Regarding the 5-year composite of cardiovascular death or MI, the routine invasive strategy was associated with a lower hazard in patients aged 65-74 years (HR 0.72, 95% CI 0.58 to 0.90) and those aged ≥75 years (HR 0.71, 95% CI 0.55 to 0.91), but not in those aged <65 years (HR 1.11, 95% CI 0.90 to 1.38), p=0.001 for interaction between treatment strategy and age. The interaction was driven by an excess of early MIs in patients <65 years of age; there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p=0.009 for interaction). After adjustment for other clinical risk factors the HRs remained similar.

    Conclusion

    The current analysis of the FIR dataset shows that the long-term benefit of the routine invasive strategy over the selective invasive strategy is attenuated in younger patients aged <65 years and in women by the increased risk of early events which seem to have no consequences for long-term cardiovascular mortality. No other clinical risk factors were able to identify patients with differential responses to a routine invasive strategy.

  • 280. Damman, Peter
    et al.
    de Winter, Robbert J
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fox, Keith A
    Letter by Damman et al regarding articles, "Long-term cardiovascular mortality after procedure-related or spontaneous myocardial infarction in patients with non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)" and "American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation universal definition of myocardial infarction classification system and the risk of cardiovascular death: Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38)”2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 9, p. E136-E137Article in journal (Refereed)
  • 281. Damman, Peter
    et al.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jeppsson, Anders
    Jernberg, Tomas
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Invasive Strategies And Outcomes For Non-ST-segment Elevation Acute Coronary Syndromes: A Twelve-year Experience From SWEDEHEART2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B133-B133Article in journal (Other academic)
  • 282.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    de Winter, Robbert J
    Jeppsson, Anders
    Johanson, Per
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Invasive strategies and outcomes for non-ST-segment elevation acute coronary syndromes: a twelve-year experience from SWEDEHEART.2016In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 12, no 9, p. 1108-1116Article in journal (Refereed)
    Abstract [en]

    AIMS: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice.

    METHODS AND RESULTS: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007.

    CONCLUSIONS: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.

  • 283. Damman, Peter
    et al.
    van Geloven, Nan
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fox, Keith A. A.
    Clayton, Tim
    Pocock, Stuart J.
    Hirsch, Alexander
    Windhausen, Fons
    Tijssen, Jan G. P.
    de Winter, Robbert J.
    Timing of Angiography With a Routine Invasive Strategy and Long-Term Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome: A Collaborative Analysis of Individual Patient Data From the FRISC II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) Trials2012In: JACC: Cardiovascular Interventions, ISSN 1936-8798, Vol. 5, no 2, p. 191-199Article in journal (Refereed)
    Abstract [en]

    Objectives: This study sought to investigate long-term outcomes after early or delayed angiography in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS) undergoing a routine invasive management. Background The optimal timing of angiography in patients with nSTE-ACS is currently a topic for debate.

    Methods: Long-term follow-up after early (within 2 days) angiography versus delayed (within 3 to 5 days) angiography was investigated in the FRISC-II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) (FIR) nSTE-ACS patient-pooled database. The main outcome was cardiovascular death or myocardial infarction up to 5-year follow-up. Hazard ratios (HR) were calculated with Cox regression models. Adjustments were made for the FIR risk score, study, and the propensity of receiving early angiography using inverse probability weighting.

    Results: Of 2,721 patients originally randomized to the routine invasive arm, consisting of routine angiography and subsequent revascularization if suitable, 975 underwent early angiography and 1,141 delayed angiography. No difference was observed in 5-year cardiovascular death or myocardial infarction in unadjusted (HR: 1.06, 95% confidence interval [CI]: 0.79 to 1.42, p = 0.61) and adjusted (HR: 0.93, 95% CI: 0.75 to 1.16, p = 0.54) Cox regression models.

    Conclusions: In the FIR database of patients presenting with nSTE-ACS, the timing of angiography was not related to long-term cardiovascular mortality or myocardial infarction. (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes [ICTUS]; ISRCTN82153174. Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction [the Third Randomised Intervention Treatment of Angina Trials (RITA-3)]; ISRCTN07752711)

  • 284.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Koul, Sasha
    Eriksson, Peter
    Erlinge, David
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Patient characteristics and bleeding outcomes in invasively treated acute coronary syndrome patients treated with prasugrel or clopidogrel2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 59, no 13, p. E271-E271Article in journal (Other academic)
  • 285.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Fox, Keith A. A.
    Windhausen, Fons
    Hirsch, Alexander
    Clayton, Tim
    Pocock, Stuart J.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Tijssen, Jan G. P.
    de Winter, Robbert J.
    Long-Term Cardiovascular Mortality after Procedure-Related or Spontaneous Myocardial Infarction in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome: A Collaborative Analysis of Individual Patient Data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 4, p. 568-576Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    To investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).

    METHODS AND RESULTS:

    Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient-pooled dataset of the FRISC-II, ICTUS and RITA-3 (FIR) NSTE-ACS trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated with the Kaplan-Meier method, hazard ratios (HR) were calculated with time-dependent Cox proportional-hazards models. Adjustments were made for the variables associated with long-term outcomes. Of the 5467 patients, 212 endured a procedure-related MI within 6 months after enrolment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who endured a procedure-related MI and comparable to patients without a procedure-related MI (HR 0.66, 95%CI: 0.36-1.20, P=0.17). In patients who endured a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2% and higher than patients without a spontaneous MI (HR 4.52, 95%CI: 3.37-6.06, P<0.001). These HRs did not materially alter after risk adjustments.

    CONCLUSIONS:

    Five-year follow-up of NSTE-ACS patients from the three FIR trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast there was a substantially raised long-term mortality after a spontaneous MI.

  • 286.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Woudstra, Pier
    Kuijt, Wichert J
    de Winter, Robbert J
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    P2Y12 platelet inhibition in clinical practice2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 33, no 2, p. 143-153Article in journal (Refereed)
    Abstract [en]

    Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines.

  • 287. Danad, Ibrahim
    et al.
    Uusitalo, Valtteri
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Saraste, Antti
    Raijmakers, Pieter G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lammertsma, Adriaan A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Heymans, Martijn W.
    Kajander, Sami A.
    Pietilae, Mikko
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Knaapen, Paul
    Knuuti, Juhani
    Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease Cutoff Values and Diagnostic Accuracy of Quantitative [O-15]H2O PET Imaging2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 64, no 14, p. 1464-1475Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. OBJECTIVES The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [O-15]H2O positron emission tomography (PET). METHODS A total of 330 patients underwent both quantitative [O-15]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve <= 0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. RESULTS Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 +/- 0.25 and 0.92 +/- 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 +/- 1.04 ml/min/g and 1.73 +/- 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. CONCLUSIONS Quantitative MBF measurements with the use of [O-15]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

  • 288. Danaei, Goodarz
    et al.
    Fahimi, Saman
    Lu, Yuan
    Zhou, Bin
    Hajifathalian, Kaveh
    Di Cesare, Mariachiara
    Lo, Wei-Cheng
    Reis-Santos, Barbara
    Cowan, Melanie J.
    Shaw, Jonathan E.
    Bentham, James
    Lin, John K.
    Bixby, Honor
    Magliano, Dianna
    Bovet, Pascal
    Miranda, J. Jaime
    Khang, Young-Ho
    Stevens, Gretchen A.
    Riley, Leanne M.
    Ali, Mohammed K.
    Ezzati, Majid
    Abdeen, Ziad A.
    Kadir, Khalid Abdul
    Abu-Rmeileh, Niveen M.
    Acosta-Cazares, Benjamin
    Aekplakorn, Wichai
    Aguilar-Salinas, Carlos A.
    Ahmadvand, Alireza
    Al Nsour, Mohannad
    Alkerwi, Ala'a
    Amouyel, Philippe
    Andersen, Lars Bo
    Anderssen, Sigmund A.
    Andrade, Dolores S.
    Anjana, Ranjit Mohan
    Aounallah-Skhiri, Hajer
    Aris, Tahir
    Arlappa, Nimmathota
    Arveiler, Dominique
    Assah, Felix K.
    Avdicova, Maria
    Balakrishna, Nagalla
    Bandosz, Piotr
    Barbagallo, Carlo M.
    Barcelo, Alberto
    Batieha, Anwar M.
    Baur, Louise A.
    Ben Romdhane, Habiba
    Bernabe-Ortiz, Antonio
    Bhargava, Santosh K.
    Bi, Yufang
    Bjerregaard, Peter
    Bjorkelund, Cecilia
    Blake, Margaret
    Blokstra, Anneke
    Bo, Simona
    Boehm, Bernhard O.
    Boissonnet, Carlos P.
    Brajkovich, Imperia
    Breckenkamp, Juergen
    Brewster, Lizzy M.
    Brian, Garry R.
    Bruno, Graziella
    Bugge, Anna
    de Leon, Antonio Cabrera
    Can, Gunay
    Candido, Ana Paula C.
    Capuano, Vincenzo
    Carvalho, Maria J.
    Casanueva, Felipe F.
    Caserta, Carmelo A.
    Castetbon, Katia
    Chamukuttan, Snehalatha
    Chaturvedi, Nishi
    Chen, Chien-Jen
    Chen, Fangfang
    Chen, Shuohua
    Cheng, Ching-Yu
    Chetrit, Angela
    Chiou, Shu-Ti
    Cho, Yumi
    Chudek, Jerzy
    Cifkova, Renata
    Claessens, Frank
    Concin, Hans
    Cooper, Cyrus
    Cooper, Rachel
    Costanzo, Simona
    Cottel, Dominique
    Cowell, Chris
    Crujeiras, Ana B.
    D'Arrigo, Graziella
    Dallongeville, Jean
    Dankner, Rachel
    Dauchet, Luc
    de Gaetano, Giovanni
    De Henauw, Stefaan
    Deepa, Mohan
    Dehghan, Abbas
    Dhana, Klodian
    Di Castelnuovo, Augusto F.
    Djalalinia, Shirin
    Doua, Kouamelan
    Drygas, Wojciech
    Du, Yong
    Egbagbe, Eruke E.
    Eggertsen, Robert
    El Ati, Jalila
    Elosua, Roberto
    Erasmus, Rajiv T.
    Erem, Cihangir
    Ergor, Gul
    Eriksen, Louise
    la Penaa, Jorge Escobedo-De
    Fall, Caroline H.
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Fernandez-Berges, Daniel
    Ferrari, Marika
    Ferreccio, Catterina
    Finn, Joseph D.
    Foger, Bernhard
    Foo, Leng Huat
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Frontera, Guillermo
    Furusawa, Takuro
    Gaciong, Zbigniew
    Galbarczyk, Andrzej
    Garnett, Sarah P.
    Gaspoz, Jean-Michel
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Ghasemain, Anoosheh
    Giampaoli, Simona
    Gianfagna, Francesco
    Giovannelli, Jonathan
    Gross, Marcela Gonzalez
    Rivas, Juan P. Gonzalez
    Gorbea, Mariano Bonet
    Gottrand, Frederic
    Grant, Janet F.
    Grodzicki, Tomasz
    Grontved, Anders
    Gruden, Grabriella
    Gu, Dongfeng
    Guan, Ong Peng
    Guerrero, Ramiro
    Guessous, Idris
    Guimaraes, Andre L.
    Gutierrez, Laura
    Hardy, Rebecca
    Kumar, Rachakulla Hari
    He, Jiang
    Heidemann, Christin
    Hihtaniemi, Ilpo Tapani
    Ho, Sai Yin
    Ho, Suzanne C.
    Hofman, Albert
    Russo, Andrea R. V.
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Houti, Leila
    Hussieni, Abdullatif S.
    Huybrechts, Inge
    Hwalla, Nahla
    Iacoviello, Licia
    Iannone, Anna G.
    Ibrahim, Mohsen M.
    Ikeda, Nayu
    Ikram, M. Arfan
    Irazola, Vilma E.
    Islam, Muhammad
    Iwasaki, Masanori
    Jacobs, Jeremy M.
    Jafar, Tazeen
    Jasienska, Grazyna
    Jiang, Chao Qiang
    Jonas, Jost B.
    Joshi, Pradeep
    Kafatos, Anthony
    Kalter-Leibovici, Ofra
    Kasaeian, Amir
    Katz, Joanne
    Kaur, Prabhdeep
    Kavousi, Maryam
    Kelishadi, Roya
    Kengne, Andre P.
    Kersting, Mathilde
    Khader, Yousef Saleh
    Kiechl, Stefan
    Kim, Jeongseon
    Kiyohara, Yutaka
    Kolsteren, Patrick
    Korrovits, Paul
    Koskinen, Seppo
    Kratzer, Wolfgang
    Kromhout, Daan
    Kula, Krzysztof
    Kurjata, Pawel
    Kyobutungi, Catherine
    Lachat, Carl
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Laxmaiah, Avula
    Leclercq, Catherine
    Lee, Jeannette
    Lee, Jeonghee
    Lehtimaki, Terho
    Lekhraj, Rampal
    Leon-Munoz, Luz M.
    Li, Yanping
    Lim, Wei-Yen
    Lima-Costa, M. Fernanda
    Lin, Hsien-Ho
    Lin, Xu
    Lissner, Lauren
    Lorbeer, Roberto
    Lozano, Jose Eugenio
    Lundqvist, Annamari
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Ma, Guansheng
    Machado-Coelho, George L. L.
    Machi, Suka
    Maggi, Stefania
    Makdisse, Marcia
    Rao, Kodavanti Mallikharjuna
    Manios, Yannis
    Manzato, Enzo
    Margozzini, Paula
    Marques-Vidal, Pedro
    Martorell, Reynaldo
    Masoodi, Shariq R.
    Matsha, Tandi E.
    Mbanya, Jean Claude N.
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    McLachlan, Stela
    McNulty, Breige A.
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Menezes, Ana Maria B.
    Merat, Shahin
    Meshram, Indrapal I.
    Mi, Jie
    Miquel, Juan Francisco
    Mohamed, Mostafa K.
    Mohammad, Kazem
    Mohan, Viswanathan
    Yusoff, Muhammad Fadhli Mohd
    Moller, Niels C.
    Molnar, Denes
    Mondo, Charles K.
    Moreno, Luis A.
    Morgan, Karen
    Moschonis, George
    Mossakowska, Malgorzata
    Mostafa, Aya
    Mota, Jorge
    Muiesan, Maria L.
    Muller-Nurasyid, Martina
    Mursu, Jaakko
    Nagel, Gabriele
    Namesna, Jana
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Navarrete-Munoz, Eva Maria
    Ndiaye, Ndeye Coumba
    Nervi, Flavio
    Nguyen, Nguyen D.
    Nieto-Martinez, Ramfi S. E.
    Ning, Guang
    Ninomiya, Toshiharu
    Noale, Marianna
    Noto, Davide
    Ochoa-Aviles, Angelica M.
    Oh, Kyungwon
    Onat, Altan
    Osmond, Clive
    Otero, Johanna A.
    Palmieri, Luigi
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Parsaeian, Mahboubeh
    Peixoto, Sergio Viana
    Pereira, Alexandre C.
    Peters, Annette
    Peykari, Niloofar
    Pilav, Aida
    Pitakaka, Freda
    Piwonska, Aleksandra
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Porta, Miquel
    Portegies, Marileen L. P.
    Poustchi, Hossein
    Pradeepa, Rajendra
    Price, Jacqueline F.
    Punab, Margus
    Qasrawi, Radwan F.
    Qorbani, Mostafa
    Raitakari, Olli
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    Ramos, Rafel
    Rampal, Sanjay
    Rathmann, Wolfgang
    Redon, Josep
    Reganit, Paul Ferdinand M.
    Rigo, Fernando
    Robinson, Sian M.
    Robitaille, Cynthia
    Rodriguez, Laura A.
    Rodriguez-Artalejo, Fernando
    Rodriguez-Perez, Maria del Cristo
    Rojas-Martinez, Rosalba
    Romaguera, Dora
    Rosengren, Annika
    Rubinstein, Adolfo
    Rui, Ornelas
    Ruiz-Betancourt, Blanca Sandra
    Rutkowski, Marcin
    Sabanayagam, Charumathi
    Sachdev, Harshpal S.
    Saidi, Olfa
    Sakarya, Sibel
    Salanave, Benoit
    Salonen, Jukka T.
    Salvetti, Massimo
    Sanchez-Abanto, Jose
    Nunes, Renata
    Santos, Rute
    Sardinha, Luis B.
    Scazufca, Marcia
    Schargrodsky, Herman
    Scheidt-Nave, Christa
    Shibuya, Kenji
    Shin, Youchan
    Shiri, Rahman
    Siantar, Rosalynn
    Sibai, Abla M.
    Simon, Mary
    Simons, Judith
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    Snijder, Marieke B.
    Solfrizzi, Vincenzo
    Sonestedt, Emily
    Soumare, Aicha
    Staessen, Jan A.
    Steene-Johannessen, Jostein
    Stehle, Peter
    Stein, Aryeh D.
    Stessman, Jochanan
    Stockl, Doris
    Stokwiszewski, Jakub
    Strufaldi, Maria Wany
    Sun, Chien-An
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Suriyawongpaisal, Paibul
    Sy, Rody G.
    Tai, E. Shyong
    Tarawneh, Mohammed
    Tarqui-Mamani, Carolina B.
    Thijs, Lutgarde
    Tolstrup, Janne S.
    Topbas, Murat
    Torrent, Maties
    Traissac, Pierre
    Trinh, Oanh T. H.
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Turley, Maria L.
    Tzourio, Christophe
    Ueda, Peter
    Ukoli, Flora M.
    Ulmer, Hanno
    Valdivia, Gonzalo
    Van Valkengoed, Irene G. M.
    Vanderschueren, Dirk
    Vanuzzo, Diego
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Veronesi, Giovanni
    Verschuren, Monique
    Vioque, Jesus
    Virtanen, Jyrki
    Visvikis-Siest, Sophie
    Viswanathan, Bharathi
    Vollenweider, Peter
    Voutilainen, Sari
    Wade, Alisha N.
    Wagner, Aline
    Walton, Janette
    Mohamud, Wan Nazaimoon Wan
    Wang, Ming-Dong
    Wang, Ya Xing
    Wannamethee, S. Goya
    Weerasekera, Deepa
    Whincup, Peter H.
    Widhalm, Kurt
    Wiecek, Andrzej
    Wilks, Rainford J.
    Willeit, Johann
    Wojtyniak, Bogdan
    Wong, Tien Yin
    Woo, Jean
    Woodward, Mark
    Wu, Aleksander Giwercman
    Wu, Frederick C.
    Wu, Shou Ling
    Xu, Haiquan
    Yang, Xiaoguang
    Ye, Xingwang
    Yoshihara, Akihiro
    Younger-Coleman, Novie O.
    Zambon, Sabina
    Zargar, Abdul Hamid
    Zdrojewski, Tomasz
    Zhao, Wenhua
    Zheng, Yingfeng
    Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants2015In: LANCET DIABETES & ENDOCRINOLOGY, ISSN 2213-8587, Vol. 3, no 8, p. 624-637Article in journal (Refereed)
    Abstract [en]

    Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.

  • 289. Dans, Antonio L
    et al.
    Connolly, Stuart J
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yang, Sean
    Nakamya, Juliet
    Brueckmann, Martina
    Ezekowitz, Michael
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eikelboom, John W
    Reilly, Paul A
    Yusuf, Salim
    Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY®) Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 127, no 5, p. 634-640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    RE-LY showed that dabigatran etexilate 150 mg bid (DE150) was superior, and 110 mg bid (DE110) non-inferior to warfarin in preventing stroke and systemic embolism (SSE) in patients with atrial fibrillation (AF). In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and didn't receive concomitant antiplatelets METHODS AND RESULTS: All comparisons used a cox proportional hazards model with adjustments made for risk factors for bleeding. A time dependent analysis was performed when comparing patients with concomitant antiplatelets to those without. 6952 of 18,113 patients (38.4%) received concomitant ASA or clopidogrel at some time during the study. DE110 was non-inferior to warfarin in reducing SSE, whether patients received antiplatelets (HR=0.93; 95%CI: 0.70-1.25) or not (HR=0.87; 95%CI: 0.66-1.15; interaction p=0.738). There were less major bleeds than warfarin in both subgroups (HR=0.82; 95%CI: 0.67-1.00 for patients who used antiplatelets; HR=0.79; 95% CI: 0.64-0.96 for patients who didn't; interaction p=0.794). DE 150 reduced the primary outcome of SSE compared to warfarin. This effect seemed attenuated among patients who used antiplatelets (HR=0.80, 95%CI: 0.59-1.08) compared to those who didn't (HR=0.52, 95%CI: 0.38-0.72; p for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR=0.93, 95%CI: 0.76-1.12 for patients who used antiplatelets; HR=0.94, 95%CI: 0.78-1.15 for patients who didn't; p for interaction=0.875). In the time dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR=1.60; 95% CI: 1.42, 1.82). Dual antiplatelet seemed to increased this even more (HR=2.31; 95% CI: 1.79, 2.98). The absolute risks were lowest on DE110 compared to DE150 or warfarin.

    CONCLUSIONS:

    Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between DE110 and DE150 requires a careful assessment of characteristics that influence the balance between benefit and harm.

  • 290.
    Darmanis, Spyros
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nong, Rachel Yuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Vänelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ericsson, Olle
    Halo Genomics AB, Dag Hammarskjölds väg 36B, SE-752 37 Uppsala Sweden.
    Fredriksson, Simon
    Olink Biosciences, Dag Hammarskjölds väg 52B, SE-752 37 Uppsala, Sweden.
    Bäcklin, Christofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gut, Marta
    Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028 Barcelona, Spain.
    Heath, Simon
    Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028 Barcelona, Spain.
    Gut, Ivo Glynne
    Centro Nacional de Análisis Genómico, C/Baldiri Reixac 4, 08028 Barcelona, Spain.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gustafsson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    ProteinSeq: high-performance proteomic analyses by proximity ligation and next generation sequencing2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 9, p. e25583-Article in journal (Refereed)
    Abstract [en]

    Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 μl of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use. 

  • 291. D'Ascenzo, Fabrizio
    et al.
    Bollati, Mario
    Clementi, Fabrizio
    Castagno, Davide
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    de la Torre Hernandez, Jose M
    Ten Berg, Juriën M
    Brodie, Bruce R
    Urban, Philip
    Jensen, Lisette Okkels
    Sardi, Gabriel
    Waksman, Ron
    Lasala, John M
    Schulz, Stefanie
    Stone, Gregg W
    Airoldi, Flavio
    Colombo, Antonio
    Lemesle, Gilles
    Applegate, Robert J
    Buonamici, Piergiovanni
    Kirtane, Ajay J
    Undas, Anetta
    Sheiban, Imad
    Gaita, Fiorenzo
    Sangiorgi, Giuseppe
    Modena, Maria Grazia
    Frati, Giacomo
    Biondi-Zoccai, Giuseppe
    Incidence and predictors of coronary stent thrombosis: Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 2, p. 575-584Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis.

    METHODS:

    PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥2000 patients undergoing stenting or reporting on ≥25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised.

    RESULTS:

    A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently.

    CONCLUSIONS:

    Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

  • 292. Davidson, Thomas
    et al.
    Husberg, Magnus
    Janzon, Magnus
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Levin, Lars-Åke
    Cost-effectiveness of dabigatran compared with warfarin for patients with atrial fibrillation in Sweden2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    Aims

    Patients with atrial fibrillation have a significantly increased risk of thromboembolic events such as ischaemic stroke, and patients are therefore recommended to be treated with anticoagulation treatment. The most commonly used anticoagulant consists of vitamin K antagonist such as warfarin. A new oral anticoagulation treatment, dabigatran, has recently been approved for stroke prevention among patients with atrial fibrillation. The purpose of this study was to estimate the cost-effectiveness of dabigatran as preventive treatment of stroke and thromboembolic events compared with warfarin in 65-year-old patients with atrial fibrillation in Sweden.

    Methods and results

    A decision analytic simulation model was used to estimate the long-term (20-year) costs and effects of the different treatments. The outcome measures are the number of strokes prevented, life years gained, and quality-adjusted life years (QALYs) gained. Costs and effect data are adjusted to a Swedish setting. Patients below 80 years of age are assumed to start with dabigatran 150 mg twice a day and switch to 110 mg twice a day at the age of 80 years due to higher bleeding risk. The price of dabigatran in Sweden is €2.82 (Swedish kronor 25.39) per day for both doses. The cost per QALY gained for dabigatran compared with warfarin is estimated at €7742, increasing to €12 449 if dabigatran is compared with only well-controlled warfarin treatment.

    Conclusion

    Dabigatran is a cost-effective treatment in Sweden, as its incremental cost-effectiveness ratio is below the normally accepted willingness to pay limit.

  • 293. De Caterina, R
    et al.
    Husted, S
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andreotti, F
    Arnesen, H
    Bachmann, F
    Baigent, C
    Huber, K
    Jespersen, J
    Kristensen, S D
    Lip, G Y H
    Morais, J
    Rasmussen, L H
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Verheugt, F W A
    Weitz, J I
    General mechanisms of coagulation and targets of anticoagulants (Section I): Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 109, no 4, p. 569-579Article in journal (Refereed)
    Abstract [en]

    Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.

  • 294.
    De Caterina, Raffaele
    et al.
    Univ G DAnnunzio, Inst Cardiol, Chieti, Italy.;Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy..
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Al-Khatib, Sana M.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Bahit, M. Cecilia
    INECO Neurociencias Orono, Rosario, Santa Fe, Argentina..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Hohnloser, Stefan
    Goethe Univ Frankfurt, Frankfurt, Germany..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA 02215 USA..
    Lanas, Fernando
    Univ La Frontera, Temuco, Chile..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Lopez-Sendon, Jose
    Hosp Univ La Paz, IdiPaz Madrid, Madrid, Spain..
    Renda, Giulia
    Univ G DAnnunzio, Inst Cardiol, Chieti, Italy.;Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy..
    Horowitz, John
    Queen Elizabeth Hosp, Adelaide, SA, Australia..
    Granger, Christopher B.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 175, p. 175-183Article in journal (Refereed)
    Abstract [en]

    Aims History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. Methods and results The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. Conclusion In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.

  • 295. De Caterina, Raffaele
    et al.
    Husted, Steen
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Agnelli, Giancarlo
    Bachmann, Fedor
    Baigent, Colin
    Jespersen, Jørgen
    Kristensen, Steen Dalby
    Montalescot, Gilles
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Verheugt, Freek W.
    Weitz, Jeffrey
    Anticoagulants in heart disease: current status and perspectives2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 7, p. 880-913Article, review/survey (Refereed)
  • 296.
    De Caterina, Raffaele
    et al.
    Univ G DAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Pisa, Italy..
    Husted, Steen
    Univ Aarhus, Aarhus, Denmark..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andreotti, Felicita
    Univ Cattolica Sacro Cuore, I-00168 Rome, Italy..
    Arnesen, Harald
    Oslo Univ Hosp Ulleval, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Bachmann, Fedor
    Univ Lausanne, Lausanne, Switzerland..
    Baigent, Colin
    Univ Oxford, Oxford, England..
    Collet, Jean-Philippe
    Grp Hosp Pitie Salpetriere, INSERM, UMRS ICAN 1166, F-75634 Paris, France..
    Halvorsen, Sigrun
    Oslo Univ Hosp Ulleval, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Huber, Kurt
    Wilhelminenhosp, Vienna, Austria..
    Jespersen, Jorgen
    Univ Southern Denmark, Esbjerg, Denmark..
    Kristensen, Steen Dalby
    Aarhus Univ Hosp, DK-8000 Aarhus, Denmark..
    Lip, Gregory Y. H.
    Univ Birmingham, City Hosp, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Morais, Joao
    Hosp Santo Andre, Leiria, Portugal..
    Rasmussen, Lars Hvilsted
    Aalborg Univ, Aalborg, Denmark..
    Ricci, Fabrizio
    Univ G DAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Pisa, Italy..
    Sibbing, Dirk
    Univ Munich, Klinikum Univ Munchen, Med Klin & Poliklin 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Storey, Robert F.
    Univ Sheffield, Sheffield, S Yorkshire, England..
    ten Berg, Jurrien
    St Antonius Hosp, Nieuwegein, Netherlands..
    Verheugt, Freek W. A.
    Onze Lieve Vrouw Hosp, Amsterdam, Netherlands..
    Weitz, Jeffrey I.
    McMaster Univ, Hamilton, ON, Canada.;Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada..
    Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2016In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, no 4, p. 685-711Article in journal (Refereed)
    Abstract [en]

    Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

  • 297. De Caterina, Raffaele
    et al.
    Husted, Steen
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andreotti, Felicita
    Arnesen, Harald
    Bachmann, Fedor
    Baigent, Colin
    Huber, Kurt
    Jespersen, Jorgen
    Kristensen, Steen Dalby
    Lip, Gregory Y. H.
    Morais, Joao
    Rasmussen, Lars Hvilsted
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Verheugt, Freek W. A.
    Weitz, Jeffrey I.
    New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes: ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease Position Paper2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 59, no 16, p. 1413-1425Article, review/survey (Refereed)
    Abstract [en]

    Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.

  • 298. De Caterina, Raffaele
    et al.
    Husted, Steen
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andreotti, Felicita
    Arnesen, Harald
    Bachmann, Fedor
    Baigent, Colin
    Huber, Kurt
    Jespersen, Jorgen
    Kristensen, Steen Dalby
    Lip, Gregory Y. H.
    Morais, Joao
    Rasmussen, Lars Hvilsted
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Verheugt, Freek W. A.
    Weitz, Jeffrey I.
    Parenteral anticoagulants in heart disease: Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 109, no 5, p. 769-786Article in journal (Refereed)
    Abstract [en]

    Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

  • 299. De Palma, Rodney
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jueni, Peter
    Cuisset, Thomas
    Will this trial change my practice?: ACCOAST - early loading with a novel P2Y12 inhibitor in patients with an acute coronary syndrome2014In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 10, no 3, p. 408-410Article in journal (Other academic)
  • 300.
    De Silva, Kalpa
    et al.
    Kings Coll Hosp London, Dept Cardiol, London, England..
    Myat, Aung
    Brighton & Sussex Univ Hosp NHS Trust, Sussex Cardiac Ctr, Brighton, E Sussex, England.;Brighton & Sussex Med Sch, Dept Clin & Expt Med, Brighton, E Sussex, England..
    Cotton, James
    Royal Wolverhampton NHS Trust, Dept Cardiol, Heart & Lung Ctr, Wolverhampton, W Midlands, England..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gershlick, Anthony
    Univ Leicester, Dept Cardiol, Leicester, Leics, England.;NIHR Leicester Cardiovasc Biomed Res Ctr, Leicester, Leics, England..
    Stone, Gregg W.
    Columbia Univ, New York Presbyterian Hosp, Med Ctr, Dept Cardiol, 161 First Washington Ave,Herbert Irving Pavil, New York, NY 10032 USA..
    Bleeding associated with the management of acute coronary syndromes2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 7, p. 546-562Article in journal (Refereed)
3456789 251 - 300 of 1574
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf