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  • 1. Aasa, M
    et al.
    Dellborg, M
    Herlitz, Johan
    [external].
    Svensson, L
    Grip, L
    Risk Reduction for Cardiac Events After Primary Coronary Intervention Compared With Thrombolysis for Acute ST-Elevation Myocardial Infarction (Five-Year Results of the Swedish Early Decision Reperfusion Strategy [SWEDES] Trial)2010In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 106, no 12, p. 1685-1691Article in journal (Refereed)
    Abstract [en]

    Primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction compares favorably to thrombolysis. In previous studies the benefit has been restricted to the early postinfarction period with no additional risk decrease beyond this period. Long-term outcome after use of third-generation thrombolytics and modern adjunctive pharmaceutics in the 2 treatment arms has not been investigated. This study was conducted to compare 5-year outcome after updated regimens of PPCI or thrombolysis. Patients with ST-elevation myocardial infarction were randomized to enoxaparin and abciximab followed by PPCI (n = 101) or enoxaparin followed by reteplase (n = 104), with prehospital initiation of therapy in 42% of patients. Data on survival and major cardiac events were obtained from Swedish national registries after 5.3 years. PPCI resulted in a better outcome with respect to the composite of death or recurrent myocardial infarction (hazard ratio 0.54, confidence interval 0.31 to 0.95) compared to thrombolysis. This was attributed to a significant decrease in cardiac deaths (hazard ratio 0.16, confidence interval 0.04 to 0.74). The difference evolved continuously over the 5-year follow-up. After adjustment for covariates, a significant benefit remained with respect to cardiac death or recurrent infarction but not for the composite of total survival or recurrent myocardial infarction (p = 0.07). The observed differences were not seen in patients in whom therapy was initiated in the prehospital phase. In conclusion, PPCI in combination with enoxaparin and abciximab compares favorably to thrombolysis in combination with enoxaparin with a risk decrease that stretches beyond the early postinfarction period. Prehospital thrombolysis may, however, match PPCI in long-term outcome.

  • 2. Albertsson, P
    et al.
    Emanuelsson, H
    Karlsson, T
    Lamm, C
    Sandén, W
    Lagerberg, G
    Herlitz, Johan
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Morbidity and use of medical resources in patients with chest pain and normal or near normal coronary arteries. Influences of the diagnostic angiogram1997In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 79, no 3, p. 299-304Article in journal (Refereed)
    Abstract [en]

    To evaluate morbidity and use of medical resources in patients with chest pain and normal or near-normal coronary angiograms: 2,639 consecutive patients who underwent coronary angiograms due to chest pain were registered. Two years thereafter all patients who showed normal or near-normal coronary angiograms were approached with a questionnaire regarding hospitalization during the last 4 years (2 years before and 2 years after angiography). All medical files were also examined. Of the patients who underwent angiography, 163 (6%) had no significant stenoses, and of these, 113 showed complete normal angiograms and 50 showed mild (i.e. <50%) stenoses. During the 2 years before diagnostic angiogram, 66% of the patients were hospitalized compared with only 35% during 2 years after angiography (p <0.001). The reduction in hospitalization was due to curtailed utilization of medical resources for cardiac reasons; mean days in hospital was 6.6 days before angiography versus 2.8 days after (p <0.001). There were no significant differences in hospitalization when comparing patients with mild stenoses and completely normal angiograms. There were, furthermore, no differences between patients with positive or negative exercise tests. Thus, the need for hospitalization is significantly reduced after a diagnostic angiogram reveals normal or near-normal coronary arteries.

  • 3.
    Aspelin, P
    et al.
    Huddinge Univ Hosp, Stockholm, Sweden Hop Bichat, F-75877 Paris, France Linkoping Univ Hosp, S-58185 Linkoping, Sweden Dresden Univ Technol, D-8027 Dresden, Germany FranzVolhard Klin, Berlin, Germany Natl Hosp Norway, Oslo, Norway.
    Aubry, P
    Huddinge Univ Hosp, Stockholm, Sweden Hop Bichat, F-75877 Paris, France Linkoping Univ Hosp, S-58185 Linkoping, Sweden Dresden Univ Technol, D-8027 Dresden, Germany FranzVolhard Klin, Berlin, Germany Natl Hosp Norway, Oslo, Norway.
    Fransson, Sven Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Strasser, R
    Huddinge Univ Hosp, Stockholm, Sweden Hop Bichat, F-75877 Paris, France Linkoping Univ Hosp, S-58185 Linkoping, Sweden Dresden Univ Technol, D-8027 Dresden, Germany FranzVolhard Klin, Berlin, Germany Natl Hosp Norway, Oslo, Norway.
    Willenbrock, R
    Huddinge Univ Hosp, Stockholm, Sweden Hop Bichat, F-75877 Paris, France Linkoping Univ Hosp, S-58185 Linkoping, Sweden Dresden Univ Technol, D-8027 Dresden, Germany FranzVolhard Klin, Berlin, Germany Natl Hosp Norway, Oslo, Norway.
    Berg, KJ
    Nephrotoxicity in high-risk patients. A double-blind, randomized multicenter study of iso-osmolar and low-osmolar nonionic contrast media: The nephrotoxicity, high risk, iso-osmolar, contrast media (NEPHRIC) study.2002In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 90, no 6A, p. TCT367-Conference paper (Other academic)
  • 4. Bang, Casper N
    et al.
    Greve, Anders M
    La Cour, Morten
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gohlke-Bärwolf, Christa
    Ray, Simon
    Pedersen, Terje
    Rossebø, Anne
    Okin, Peter M
    Devereux, Richard B
    Wachtell, Kristian
    Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 116, no 12, p. 1840-1844Article in journal (Refereed)
    Abstract [en]

    Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.

  • 5. Blohm, M
    et al.
    Herlitz, Johan
    [external].
    Hartford, M
    Karlson, BW
    Risenfors, M
    Luepker, RV
    Sjölin, M
    Holmberg, S
    Consequences of a media campaign focusing on delay in acute myocardial infarction1992In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, ISSN 0002-914, Vol. 69, no 4, p. 411-413Article in journal (Other academic)
  • 6. Braunschweig, Frieder
    et al.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Bibra, Helene
    Olsson, Arne
    Rydén, Lars
    Långström, Bengt
    Linde, Cecilia
    Effects of biventricular pacing on myocardial blood flow and oxygen consumption using carbon-11 acetate positron emission tomography in patients with heart failure2003In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 92, no 1, p. 95-99Article in journal (Refereed)
  • 7. Cameli, Matteo
    et al.
    Righini, Francesca Maria
    Lisi, Matteo
    Bennati, Elena
    Navarri, Romina
    Lunghetti, Stefano
    Padeletti, Margherita
    Cameli, Paolo
    Tsioulpas, Charilaos
    Bernazzali, Sonia
    Maccherini, Massimo
    Sani, Guido
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mondillo, Sergio
    Comparison of Right Versus Left Ventricular Strain Analysis as a Predictor of Outcome in Patients With Systolic Heart Failure Referred for Heart Transplantation2013In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 112, no 11, p. 1778-1784Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to explore the relation between right ventricular (RV) and left ventricular (LV) echocardiographic parameters with clinical outcome in patients with advanced heart failure referred for cardiac transplantation. Ninety-eight consecutive patients with advanced systolic heart failure, referred for cardiac transplant evaluation, were enrolled. All patients were prospectively followed for the development of new outcome events, which included hospitalization for acute heart failure, cardiovascular death, heart transplantation, intra-aortic balloon pump implantation, and ventricular assist device implantation. Conventional transthoracic echocardiography was performed in all subjects. RV longitudinal strain (RVLS) by speckle-tracking echocardiography was assessed by averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). LV global longitudinal and global circumferential strains were also calculated. Of the 98 subjects at baseline, 46 had 67 new events during a mean follow-up of 1.5 +/- 0.9 years. Free-wall RVLS, global RVLS, N-terminal fragment of the prohormone brain natriuretic peptide, RV fractional area change, and LV end-diastolic volume were independently predictive of combined outcomes (all p<0.0001). The overall performance for the prediction of cardiovascular events was greatest for free-wall RVLS (area under the curve free-wall RVLS: 0.87; global RVLS: 0.67; RV fractional area change: 0.60; N-terminal fragment of the prohormone brain natriuretic peptide, 0.62; global circumferential strain: 0.55; global longitudinal strain: 0.35; and LV ejection fraction: 0.26). Free-wall RVLS showed the highest adjusted hazards ratio. A graded association between the grade of RV dysfunction and the risk of cardiovascular events was only evident for free-wall RVLS and global RVLS. In conclusion, in patients referred for heart transplantation, RVLS is a stronger predictor of outcome than LV longitudinal strain and other conventional parameters, providing a stronger prognostic stratification.

  • 8.
    Carlhäll, Carljohan
    et al.
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Jurkevicius, R.
    Institute of Cardiology of Kaunas Medical University, Kaunas, Lithuania.
    Is left ventricular postsystolic long-axis shortening a marker for severity of hypertensive heart disease?2003In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 91, no 12, p. 1490-1493Article in journal (Refereed)
    Abstract [en]

    No abstract available.

  • 9. Chinali, Marcello
    et al.
    Aurigemma, Gerard P
    de Simone, Giovanni
    Mishra, Rakesh K
    Gerdts, Eva
    Wachtell, Kristian
    Boman, Kurt
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Dahlöf, Björn
    Devereux, Richard B
    Mitral E wave deceleration time to peak E velocity ratio and cardiovascular outcome in hypertensive patients during antihypertensive treatment (from the LIFE echo-substudy).2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 104, no 8, p. 1098-1104Article in journal (Refereed)
    Abstract [en]

    The early mitral flow deceleration time (DTE) is a prognostically validated marker of left ventricular diastolic dysfunction. It has been reported that the DTE is influenced by the loading conditions, which can vary during antihypertensive treatment. We hypothesized that normalization of the DTE for mitral peak E-velocity (mitral deceleration index [MDI]) might better predict incident cardiovascular (CV) events in hypertensive patients during treatment compared to DTE alone or other traditional indexes of diastolic function, such as the mitral E/A ratio. We evaluated 770 hypertensive patients with electrocardiogram findings of left ventricular hypertrophy (age 66 +/- 7 years; 42% women) enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. Echocardiographic examinations were performed annually for 5 years during intensive antihypertensive treatment. We examined the utility of the MDI at baseline and as a time-varying predictor of incident CV events. Of the 770 patients, 70 (9%) had CV events. The baseline MDI was positively associated with age and relative wall thickness and negatively associated with gender and heart rate (all p <0.01). Unadjusted Cox regression analysis showed a positive association between the baseline MDI and CV events (hazard ratio 1.21, 95% confidence interval 1.07 to 1.37, p = 0.002). In the time-varied Cox models, a greater in-treatment MDI was associated with a greater rate of CV events (hazard ratio 1.43, 95% confidence interval 1.05 to 1.93, p = 0.022), independently of the covariates. No significant association was found for in-treatment DTE or any of the prognostically validated indexes of diastolic function. In conclusion, in our population of patients with treated hypertension with electrocardiographic findings of left ventricular hypertrophy, the MDI independently predicted future CV events. Normalization of DTE for E velocity might be preferred to other traditional diastolic function indexes in evaluating diastolic function during antihypertensive treatment.

  • 10. 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.

  • 11.
    Damman, Peter
    et al.
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Holmvang, Lene
    Copenhagen Univ Hosp, Ctr Heart, Copenhagen, Denmark.
    Tijssen, Jan G P
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Clayton, Tim C
    London Sch Hyg & Trop Med, London WC1, England.
    Pocock, Stuart J
    London Sch Hyg & Trop Med, London WC1, England.
    Windhausen, Fons
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Hirsch, Alexander
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Fox, Keith A A
    Royal Infirm, Dept Med & Radiol Sci, Edinburgh, Midlothian, Scotland.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    de Winter, Robbert J
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Usefulness of the Admission Electrocardiogram to Predict Long-Term Outcomes After Non-ST-Elevation Acute Coronary Syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials)2012In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 109, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.

  • 12.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Koul, Sasha
    Eriksson, Peter
    Erlinge, David
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 13. Damman, Peter
    et al.
    Varenhorst, Christoph
    Koul, Sasha
    Eriksson, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, University Hospital.
    Erlinge, David
    Lagerqvist, Bo
    James, Stefan K.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 14.
    Daniel, Maria
    et al.
    Karolinska Institutet, Stockholm.
    Agewall, Stefan
    Karolinska Institutet, Stockholm.
    Caidahl, Kenneth
    Karolinska Institutet, Stockholm.
    Collste, Olov
    Karolinska Institutet, Stockholm.
    Ekenbäck, Christina
    Karolinska Institutet, Stockholm.
    Frick, Mats
    Karolinska Institutet, Stockholm.
    Y-Hassan, Shams
    Karolinska Institutet, Stockholm.
    Henareh, Logman
    Karolinska Institutet, Stockholm.
    Jernberg, Tomas
    Karolinska Institutet, Stockholm.
    Malmqvist, Karin
    Karolinska Institutet, Stockholm.
    Schenck-Gustafsson, Karin
    Karolinska Institutet, Stockholm.
    Sörensson, Peder
    Karolinska Institutet, Stockholm.
    Sundin, Örjan
    Mid Sweden University, Faculty of Human Sciences, Department of Psychology.
    Hofman-Bang, Claes
    Karolinska Institutet, Stockholm.
    Tornvall, Per
    Karolinska Institutet, Stockholm.
    Effect of Myocardial Infarction With Nonobstructive Coronary Arteries on Physical Capacity and Quality-of-Life2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 120, no 3, p. 341-346Article in journal (Refereed)
    Abstract [en]

    Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), including Takotsubo syndrome (TS), are considered to have a better survival compared with those with coronary heart disease (CHD). Studies of patients with MINOCA measuring physical and mental function including matched control groups are lacking. The aim of this study was to determine the physical capacity and quality of life in patients with MINOCA. One-hundred patients with MINOCA along with TS (25%) were investigated from 2007 to 2011. A bicycle exercise stress test was performed 6 weeks after hospitalization and QoL was investigated by the Short Form Survey 36 at 3 months' follow-up. Both a healthy and a CHD group that were age and gender matched were used as controls. The MINOCA group had a lower physical capacity (139 ± 42 W) compared with the healthy control group (167 ± 53 W, p <0.001) but better than the CHD control group (124 ± 39 W, p = 0.023). Patients with MINOCA had lower physical and mental component summary scores compared with the healthy controls (p <0.001) and lower mental component summary (p = 0.012), mental health (p = 0.016), and vitality (p = 0.008) scores compared with the CHD controls. In conclusion, the findings of this first study on exercise capacity and QoL in patients with MINOCA showed both physical and mental distress from 6 weeks to 3 months after the acute event similar to CHD controls and in some perspectives even lower scores especially in the mental component of QoL.

  • 15.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Will the universal definition of myocardial infarction criteria result in an overdiagnosis of myocardial infarction?2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 103, no 5, p. 588-591Article in journal (Refereed)
    Abstract [en]

    The Universal Definition of Myocardial Infarction (acute myocardial infarction [AMI]) requires detection of increasing or decreasing cardiac biomarkers (preferably cardiac troponin) with >or=1 value >99(th) percentile, together with either clinical symptoms, new ischemic electrocardiographic changes, or typical imaging findings indicative of myocardial necrosis as diagnostic criteria for AMI. However, a small cardiac troponin elevation together with ST-T segment abnormalities may also occur in clinically stable populations. Accordingly, 0.6% of elderly subjects from a community sample (PIVUS Study) and 6.7% of patients stabilized after an acute coronary syndrome (FRISC II Study) would have been labeled AMI following the Universal Definition of AMI when diagnostic classification had been based on a single cardiac troponin I result. In conclusion, our results emphasized the importance of a significant change in cardiac troponin to avoid misdiagnosis of AMI.

  • 16.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    B-type natriuretic peptides and their relation to cardiovascular structure and function in a population-based sample of subjects aged 70 years2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 103, no 7, p. 1032-1038Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate whether B-type natriuretic peptides (BNPs) could serve as screening markers for the detection of preclinical vascular disease in the community. BNP and N-terminal-pro-BNP were analyzed in 1,000 subjects aged 70 years participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study and were related to different measures of endothelial function and activation, arterial compliance, carotid atherosclerosis, and echocardiographic findings. The median levels were 42.0 ng/L for BNP and 110.7 ng/L for N-terminal-pro-BNP. On adjusted multivariate analysis, the 2 BNPs were related to increased left ventricular mass and impaired left ventricular systolic and diastolic function but not to any of the other assessed entities reflecting preclinical vascular disease. In conclusion, BNPs are strong markers of increased left ventricular mass and impaired cardiac performance but cannot be regarded as useful screening markers for the detection of preclinical states of vascular disease in elderly subjects.

  • 17.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Prognostic Usefulness of the Change in N-terminal pro B-type Natriuretic Peptide Levels to Predict Mortality in a Single Community Cohort Aged ≥70 Years2013In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 111, no 1, p. 131-136Article in journal (Refereed)
    Abstract [en]

    The levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) are closely related to cardiac abnormalities and adverse outcomes in the general population. However, little is known about the course of NT-proBNP levels over time, the underlying conditions, and the prognostic effect of changes. To investigate these issues, we measured the NT-proBNP levels (Elecsys 2010, Roche Diagnostics) in community-dwellers participating in the Prospective Investigation of the Vasculature in Uppsala Seniors study at 70 (n = 1,005) and 75 (n = 817) years of age. The total follow-up was 8.0 years. In subjects with available results from both examinations, the median NT-proBNP levels increased from 106 pg/ml (25th to 75th percentile 62 to 174) to 125 pg/ml (25th to 75th percentile 73-234; p <0.001). The change in NT-proBNP levels was positively and independently related to male gender, baseline information on ischemic electrocardiographic changes, renal dysfunction, impaired left ventricular ejection fraction, and intercurrent cardiovascular events (e.g., myocardial infarction, stroke, or coronary revascularization). The change in NT-proBNP levels independently predicted mortality after the measurements at 75 years of age (all-cause mortality, adjusted hazard ratio 2.4, 95% confidence interval 1.6 to 3.6; cardiovascular mortality, adjusted hazard ratio 2.3, 95% confidence interval 1.2 to 4.5). Compared to those without significant NT-proBNP changes (n = 606), subjects with increasing levels (n = 162) had markedly increased all-cause mortality (adjusted hazard ratio 4.3, 95% confidence interval 2.1 to 8.8). No subject with decreasing NT-proBNP levels (n = 49) died. In conclusion, repeat measurements of NT-proBNP might add useful information to the routine clinical assessment in subjects aged ≥70 years, because changes in their levels were associated with cardiovascular risk indicators and strongly predictive of mortality.

  • 18. Einarsen, Eigir
    et al.
    Cramariuc, Dana
    Lønnebakken, Mai T
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gohlke-Bärwolf, Christa
    Chambers, John B
    Gerdts, Eva
    Comparison of frequency of ischemic cardiovascular events in patients with aortic stenosis with versus without asymmetric septal hypertrophy (from the SEAS Trial)2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 7, p. 1082-1087Article in journal (Refereed)
    Abstract [en]

    Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3 years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p = 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p = 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.

  • 19.
    Elde, Leslie S.P.
    et al.
    University of Bergen, Bergen, Norway.
    Ranhoff, Anette H.
    University of Bergen, Bergen, Norway & Haraldsplass Hospital, Bergen, Norway.
    Fridlund, Bengt
    Jönköping University, School of Health Science, HHJ, Dep. of Nursing Science. Jönköping University, School of Health Science, HHJ. ADULT.
    Haaverstad, Rune
    University of Bergen, Bergen, Norway & Haukeland University Hospital, Bergen, Norway.
    Hufthammer, Karl Ove
    Haukeland University Hospital, Bergen, Norway.
    Kuiper, Karel K.J.
    Haukeland University Hospital, Bergen, Norway.
    Nordrehaug, Jan Erik
    University of Bergen, Bergen, Norway & Stavanger University Hospital, Stavanger, Norway.
    Norekvål, Tone M.
    University of Bergen, Bergen, Norway & Haukeland University Hospital, Bergen, Norway.
    Comparison of frequency, risk factors, and time course of postoperative delirium in octogenarians after transcatheter aortic valve implantation versus surgical aortic valve replacement2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 6, p. 802-809Article in journal (Refereed)
  • 20. Engdahl, J
    et al.
    Bång, A
    [external].
    Lindqvist, J
    Herlitz, Johan
    [external].
    Can we define patients with no and those with some chance of survival when found in asystole out of hospital?2000In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 86, no 6, p. 610-614Article in journal (Refereed)
    Abstract [en]

    We describe the epidemiology, prognosis, and circumstances at resuscitation among a consecutive population of patients with out-of-hospital cardiac arrest (OHCA) with asystole as the arrhythmia first recorded by the Emergency Medical Service (EMS), and identify factors associated with survival. We included all patients in the municipality of Göteborg, regardless of age and etiology, who experienced an OHCA between 1981 and 1997. There were a total of 4,662 cardiac arrests attended by the EMS during the study period. Of these, 1,635 (35%) were judged as having asystole as the first-recorded arrhythmia: 156 of these patients (10%) were admitted alive to hospital, and 32 (2%) were discharged alive. Survivors were younger (median age 58 vs 68 years) and had a witnessed cardiac arrest more often than nonsurvivors (78% vs 50%). Survivors also had shorter intervals from collapse to arrival of ambulance (3.5 vs 6 minutes) and the mobile coronary care unit (MCCU) (5 vs 10 min), and they received atropine less often on scene. There were also a greater proportion of survivors with noncardiac etiologies of cardiac arrest (48% vs 27%). Survivors to discharge also displayed higher degrees of consciousness on arrival to the emergency department in comparison to nonsurvivors. Multivariate analysis among all patients with asystole indicated age (p = 0.01) and witnessed arrest (p = 0.03) as independent predictors of an increased chance of survival. Multivariate analysis among witnessed arrests indicated short time to arrival of the MCCU (p < 0.001) and no treatment with atropine (p = 0.05) as independent predictors of survival. Fifty-five percent of patients discharged alive had none or small neurologic deficits (cerebral performance categories 1 or 2). No patients > 70 years old with unwitnessed arrests (n = 211) survived to discharge.

  • 21. Ezekowitz, Michael D.
    et al.
    Reilly, Paul A.
    Nehmiz, Gerhard
    Simmers, Timothy A.
    Nagarakanti, Rangadham
    Parcham-Azad, Kambiz
    Pedersen, K. Erik
    Lionetti, Dominick A.
    Stangier, Joachim
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study)2007In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 100, no 9, p. 1419-1426Article in journal (Refereed)
    Abstract [en]

    This is the first evaluation of dabigatran, an oral direct thrombin inhibitor, in patients with atrial fibrillation (AF). Patients (n = 502) were randomized to receive blinded doses of 50-, 150-, or 300-mg dabigatran twice daily alone or combined with 81- or 325-mg aspirin or open-label warfarin administered to achieve an international normalized ratio of 2 to 3 for 12 weeks. Dabigatran plasma concentrations, activated partial thromboplastin time, D-dimer, urinary 11-dehydrothromboxane B(2) (DTB2), and liver function were measured at baseline and at 1, 2, 4, 8, and 12 weeks. Clinical end points were assessed according to the treatment received at the time of the event. Overall, 92% of patients completed the study. Major hemorrhages were limited to the group treated with 300-mg dabigatran plus aspirin (4 of 64), and the incidence was significant versus 300-mg dabigatran alone (0 of 105, p <0.02). Total bleeding events were more frequent in the 300-mg (39 of 169, 23%) and 150-mg (30 of 169, 18%) dabigatran groups compared with the 50-mg groups (7 of 107, 7%; p = 0.0002 and p = 0.01, respectively). Thromboembolic events were limited to the 50-mg dabigatran dose groups (2 of 107, 2%). The mean trough d-dimer measurements were suppressed for the 2 highest doses of dabigatran and warfarin (international normalized ratio of 2 to 3). Aminotransferase levels >3 times the upper limit of normal were observed in 0.9% of the dabigatran recipients and in none of the warfarin recipients. Two dabigatran recipients had aminotransferase levels >5 times the upper limit of normal as a result of gallstones, which resolved. Trough activated partial thromboplastin time values were 1.2, 1.5, and 1.8 times the baseline level for the 50-, 150-, and 300-mg dabigatran groups, respectively. DTB2 concentrations after 12 weeks of 50-, 150-, and 300-mg dabigatran treatment were increased by 31%, 17%, and 23%, respectively, versus baseline (p = 0.02, p = 0.03, and p = 0.0004). In conclusion, major bleeding events were limited to patients treated with dabigatran 300 mg plus aspirin and thromboembolic episodes were limited to the 50-mg dabigatran groups. The 2 highest doses of dabigatran suppress D-dimer concentrations. Serious liver toxicity was not seen. The significance of the increase of DTB2 concentrations in dabigatran-treated patients needs resolution.

  • 22.
    Gaglia, Michael A., Jr.
    et al.
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Lipinski, Michael J.
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Lhermusier, Thibault
    Ctr Hosp Univ Toulouse, Div Cardiol, Toulouse, France..
    Steinvil, Arie
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Kiramijyan, Sarkis
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Pokharel, Shreejana
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Torguson, Rebecca
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Angiolillo, Dominick J.
    Univ Florida, Coll Med Jacksonville, Div Cardiol, Jacksonville, FL USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Storey, Robert F.
    Univ Sheffield, Div Cardiol, Sheffield, S Yorkshire, England..
    Waksman, Ron
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Comparison of Platelet Reactivity in Black Versus White Patients With Acute Coronary Syndromes After Treatment With Ticagrelor2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 8, p. 1135-1140Article in journal (Refereed)
    Abstract [en]

    Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily. Assays included light transmission aggregometry, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein. We provided comparison with a historical white cohort. Platelet reactivity among blacks with ACS on ticagrelor was similar to that in whites, except that blacks had lower values at 4 hours, 8 hours, and on maintenance therapy for light transmission aggregometry with 20 mu mol/L adenosine diphosphate. Among blacks, high-on-treatment platelet reactivity for all 3 assays was uncommon at 1 hour and nonexistent at 4 hours, 8 hours, and while on maintenance therapy. Blacks preloaded with clopidogrel (n = 17) had significantly lower results of VerifyNow (64 +/- 65 vs 198 +/- 86, p<0.001) and vasodilator-stimulated phosphoprotein (12.8 +/- 21.6 vs 58.9 +/- 19.9, p<0.001) at 1 hour compared with those with no clopidogrel prelOad. In conclusion, among patients with ACS receiving ticagrelor, levels of platelet reactivity in blacks are similar to that in whites. This suggests that the cardiovascular benefits of ticagrelor observed in the platelet inhibition and patient outcomes (PLATO) trial are likely to be observed in blacks and whites.

  • 23. Gerdts, Eva
    et al.
    Rossebø, Anne Bjørhovde
    Pedersen, Terje Rolf
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Brudi, Philippe
    Chambers, John Boyd
    Egstrup, Kenneth
    Gohlke-Bärwolf, Christa
    Holme, Ingar
    Kesäniemi, Y Antero
    Malbecq, William
    Nienaber, Christoph
    Ray, Simon
    Skjærpe, Terje
    Wachtell, Kristian
    Willenheimer, Ronnie
    Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study)2010In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 106, no 11, p. 1634-1639Article in journal (Refereed)
    Abstract [en]

    Retrospective studies have suggested a beneficial effect of lipid-lowering treatment on the progression of aortic stenosis (AS) in milder stages of the disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 4.3 years of combined treatment with simvastatin 40 mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic cardiovascular events (ICEs) were significantly reduced in the overall study population. However, the impact of baseline AS severity on treatment effect has not been reported. Baseline and outcomes data in 1,763 SEAS patients (mean age 67 years, 39% women) were used. The study population was divided into tertiles of baseline peak aortic jet velocity (tertile 1: <= 2.8 m/s; tertile 2: >2.8 to 3.3 m/s; tertile 3: >3.3 m/s). Treatment effect and interaction were tested in Cox regression analyses. The rates of AVEs and ICEs increased with increasing baseline severity of AS. In Cox regression analyses, higher baseline peak aortic jet velocity predicted higher rates of AVEs and ICEs in all tertiles (all p values <0.05) and in the total study population (p <0.001). Simvastatin-ezetimibe treatment was not associated with a statistically significant reduction in AVEs in any individual tertile. A significant quantitative interaction between the severity of AS and simvastatin-ezetimibe treatment effect was demonstrated for ICEs (p <0.05) but not for AVEs (p = 0.10). In conclusion, the SEAS study results demonstrate a strong relation between baseline the severity of AS and the rate of cardiovascular events but no significant effect of lipid-lowering treatment on AVEs, even in the group with the mildest AS.

  • 24.
    Gotto, AM
    et al.
    Care Of Jou J, Cornell Univ, Weill Med Coll, New York, NY 10021 USA Linkoping Univ Hosp, Clin Res Ctr, S-58185 Linkoping, Sweden.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    A symposium: In Search of the Ideal Lipid-Lowering Agent - Introduction2001In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 87, no 5A, p. 1B-1BOther (Other academic)
  • 25. Greve, Anders M.
    et al.
    Bang, Casper N.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Egstrup, Kenneth
    Forman, Julie L.
    Kesäniemi, Y. Antero
    Ray, Simon
    Pedersen, Terje R.
    Best, Patricia
    Rajamannan, Nalini M.
    Wachtell, Kristian
    Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study)2018In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 121, no 6, p. 739-745Article in journal (Refereed)
    Abstract [en]

    Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p >= 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p In conclusion, in a non prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677). 

  • 26. Greve, Anders M.
    et al.
    Dalsgaard, Morten
    Bang, Casper N.
    Egstrup, Kenneth
    Rossebø, Anne B.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cramariuc, Dana
    Nienaber, Christoph A.
    Ray, Simon
    Gohlke-Baerwolf, Christa
    Okin, Peter M.
    Devereux, Richard B.
    Køber, Lars
    Wachtell, Kristian
    Usefulness of the electrocardiogram in predicting cardiovascular mortality in asymptomatic adults with aortic stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis study)2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 114, no 5, p. 751-756Article in journal (Refereed)
    Abstract [en]

    Hypertension and coronary heart disease are common in aortic stenosis (AS) and may impair prognosis for similar AS severity. Different changes in the electrocardiogram may be reflective of the separate impacts of AS, hypertension, and coronary heart disease, which could lead to enhanced risk stratification in AS. The aim of this study was therefore to examine if combining prognostically relevant electrocardiographic (ECG) findings improves prediction of cardiovascular mortality in asymptomatic AS. All patients with baseline electrocardiograms in the SEAS study were included. The primary end point was cardiovascular death. Backward elimination (p > 0.01) identified heart rate, Q waves, and Cornell voltage-duration product as independently associated with cardiovascular death. Multivariate logistic and Cox regression models were used to evaluate if these 3 ECG variables improved prediction of cardiovascular death. In 1,473 patients followed for a mean of 4.3 years (6,362 patient-years of follow-up), 70 cardiovascular deaths (5%) occurred. In multivariate analysis, heart rate (hazard ratio [FIR] 1.5 per 11.2 minute(-1) [1 SD], 95% confidence interval [CI] 1.2 to 1.8), sum of Q-wave amplitude (HR 1.3 per 2.0 nun [1 SD], 95% CI 1.1 to 1.6), and Cornell voltage-duration product (FIR 1.4 per 763 mm x ms [1 SD], 95% CI 1.2 to 1.7) remained independently associated with cardiovascular death. Combining the prognostic information contained in each of the 3 ECG variables improved integrated discrimination for prediction of cardiovascular death by 2.5%, net reclassification by 14.3%, and area under the curve by 0.06 (all p <= 0.04) beyond other important risk factors. ECG findings add incremental predictive information for cardiovascular mortality in asymptomatic patients with AS.

  • 27. Greve, Anders M.
    et al.
    Gerdts, Eva
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gohlke-Baerwolf, Christa
    Rossebo, Anne B.
    Hammer-Hansen, Sophia
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Differences in Cardiovascular Risk Profile Between Electrocardiographic Hypertrophy Versus Strain in Asymptomatic Patients With Aortic Stenosis (from SEAS Data)2011In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 108, no 4, p. 541-547Article in journal (Refereed)
    Abstract [en]

    Electrocardiograms are routinely obtained in clinical follow-up of patients with asymptomatic aortic stenosis (AS). The association with aortic valve, left ventricular (LV) response to long-term pressure load, and clinical covariates is unclear and the clinical value is thus uncertain. Data from clinical examination, electrocardiogram, and echocardiogram in 1,563 patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used. Electrocardiograms were Minnesota coded for arrhythmias and atrioventricular and intraventricular blocks; LV hypertrophy was assessed by Sokolow-Lyon voltage and Cornell voltage duration criteria; and strain by T-wave inversion and ST-segment depression. Degree of AS severity was evaluated by echocardiography as peak aortic jet velocity and LV mass was indexed by body surface area. After adjustment for age, gender, LV mass index, heart rate, systolic and diastolic blood pressures, blood glucose, digoxin, antiarrhythmic drugs, drugs acting on the renin angiotensin system, diuretics, beta blockers and calcium receptor blockers; peak aortic jet velocity was significantly greater in patients with electrocardiographic strain (mean difference 0.13 m/s, p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria (mean difference 0.12 m/s, p = 0.004). After similar adjustment, LV mass index was significantly greater in patients with electrocardiographic strain (mean difference 14.8 g/cm(2), p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria (mean differences 8.8 and 17.8 g/cm(2), respectively, p <0.001 for the 2 comparisons). In multiple comparisons patients with electrocardiographic strain had increased peak aortic jet velocity, blood glucose, and uric acid, whereas patients with LV hypertrophy by Sokolow-Lyon voltage criteria were younger and patients with LV hypertrophy by Cornell voltage duration criteria more often were women. In conclusion, electrocardiographic criteria for LV hypertrophy and strain are independently associated with peak aortic jet velocity and LV mass index. Moreover, clinical covariates differ significantly between patients with electrocardiographic strain and those with LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria. 

  • 28.
    Gripeteg, Lena
    et al.
    University of Gothenburg.
    Arvidsson, Daniel
    University of Gothenburg.
    Johannesson, Elias
    University of Gothenburg.
    Larsson, Christel
    University of Gothenburg.
    Sjöberg, Agneta
    University of Gothenburg.
    Angerås, Oskar
    University of Gothenburg.
    Fagman, Erika
    University of Gothenburg.
    Brandberg, John
    University of Gothenburg.
    Ekblom, Örjan
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Bergström, Göran
    University of Gothenburg.
    Börjesson, Mats
    University of Gothenburg.
    Concomitant Associations of Healthy Food Intake and Cardiorespiratory Fitness With Coronary Artery Calcium.2018In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 122, no 4, p. 560-564, article id S0002-9149(18)31060-9Article in journal (Refereed)
    Abstract [en]

    Conflicting findings remain regarding associations between lifestyle behaviors and coronary artery calcium (CAC). We investigated concomitant associations of healthy food intake and cardiorespiratory fitness (CRF) with CAC. Data from 706 men and women 50 to 64 years old from the Swedish SCAPIS pilot trial were analyzed. A CAC score was calculated using the Agatston method. A Healthy Food Index (HFI) was established using data from a web-based food frequency questionnaire. CRF was assessed from a bike exercise test. Regression analyses were performed with occurrence of CAC (dichotomous) and level of CAC score in patients with CAC (continuous) as outcomes. 58% had 0 CAC score. HFI was significantly associated with having no CAC (standardized coefficient β = 0.18, p <0.001) but not with level of CAC score (β = -0.09, p = 0.34). CRF showed no significant association with having no CAC (β = -0.08, p = 0.12) or with the level of CAC score (β = -0.04, p = 0.64). However, there was an interaction between HFI and CRF (β = -0.23, p = 0.02); for increasing levels of CRF there was stronger negative association between HFI and level of CAC score, reaching β = -0.48, p = 0.045 for the highest CRF level. In conclusion, these results emphasize the importance of a healthy food intake in combination with higher CRF to counteract CAC development.

  • 29.
    Hambraeus, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tydén, Patrik
    Lindahl, Bertil
    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.
    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.
    Target-Attainment Rates of Low-Density Lipoprotein Cholesterol Using Lipid-Lowering Drugs One Year After Acute Myocardial Infarction in Sweden2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 17-22Article in journal (Refereed)
    Abstract [en]

    The objective of this prospective cohort study was to describe real-life use of lipid-lowering drugs and low-density lipoprotein cholesterol (LDL-C) target-attainment rates 1 year after acute myocardial infarction (AMI). LDL-C was recorded at hospital admission for AMI and at follow-up at 2 and 12 months after AMI in 17,236 patients in the Swedish heart registry, SWEDEHEART, from 2004 through 2009. Lipid-lowering treatments were identified using the Swedish Prescribed Drug Register. More than 90% of patients received statins after ANT. Simvastatin <= 40 mg was used by 80% of patients at discharge and at 2 months and 68% at 1 year after AMI. Intensive statin therapy (LDL-C-lowering capacity >40%) was prescribed for 8.4%, 11.9%, and 12.2% at these time points, and combinations of statin/ezetimibe for 1.1%, 2.8%, and 5.0%, respectively. The LDL-C target of <2.5 mmol/L (97 mg/dl) was achieved in 74.5% of patients at 2 months and 72.3% at 12 months after AMI. Treatment was intensified for only 21.3% of patients with LDL-C above target at 2 months. In multivariate analysis, higher LDL-C levels at admission and at 2 months correlated to increased risk for under treatment at 12 months after AMI. In conclusion, statin treatment after AMI in Sweden has become standard, but titration to reach recommended LDL-C levels is still suboptimal. Strategies to further improve implementation of guidelines are needed.

  • 30. Henriksen, Egil
    et al.
    Landelius, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wesslén, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kangro, Toomas
    Jonason, Tommy
    Nyström-Rosander, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Niklasson, Urban
    Arnell, Henrik
    Rolf, Christer
    Hammarström, Eskil
    Lidell, Christer
    Ringqvist, Ivar
    Friman, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    An echocardiographic study comparing male Swedish elite orienteers with other elite endurance athletes1997In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 79, no 4, p. 521-524Article in journal (Refereed)
    Abstract [en]

    Between 1979 and 1992, there were 16 known cases of sudden unexpected cardiac death among young Swedish orienteers, whose autopsies showed myocarditis to be a common finding. Therefore, 96 elite orienteers and 47 controls underwent echocardiography, showing left ventricular wall motion abnormalities in 9% of the orienteers compared with 4% in the controls.

  • 31.
    Herlitz, Johan
    [external].
    Comparison of lisinopril versus digoxin for congestive heart failure during maintenance diuretic therapy1992In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 70, no 10, p. 84-90Article in journal (Refereed)
    Abstract [en]

    Lisinopril 5–20 mg once daily was compared with digoxin 0.125–0.375 mg once daily in a double-blind, randomized, parallel-group study involving 217 patients with mild-to-moderate heart failure (New York Heart Association [NYHA] grades II–III) who were maintained on optimized diuretic therapy. After 6 weeks of treatment, digoxin and lisinopril had increased exercise duration by 18 seconds (p = 0.015) and 32 seconds (p = 0.0007), respectively, versus the baseline run-in period. The difference between treatments was not statistically significant (p = 0.1343). After 12 weeks, digoxin and lisinopril had increased exercise duration by 29 seconds and 51 seconds, respectively. The effect of digoxin compared with the baseline value was not significant but that for lisinopril was (p = 0.0027). The difference between treatments approached statistical significance (p = 0.0813). There was no difference between lisinopril and digoxin with regard to their effects on the frequency of ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Blood pressures were not significantly different between treatments, although both systolic and diastolic blood pressure were consistently lower in the lisinopril group throughout randomized treatment. The proportions of patients demonstrating an improvement in NYHA grading were similar for both lisinopril and digoxin. Both treatments had similar effects on the symptoms of heart failure. Both drugs appeared to be equally well tolerated with a similar frequency of adverse events reported for both drugs (30% for lisinopril vs 29% for digoxin). Withdrawals from treatment were of a similar frequency for both treatments. It is concluded that lisinopril may be a useful alternative to digitalis in patients with heart failure who remain symptomatic on diuretic therapy.

  • 32.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Arrhythmias. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 35-38Article in journal (Refereed)
    Abstract [en]

    Forty-five patients in the placebo (1.5%) and 29 in the metoprolol (1%) groups, respectively, were receiving antiarrhythmic drugs on a long-term basis before entry into the trial. Before randomization, 2.2% (n = 64) of the placebo and 1.7% (n = 50) of the metoprolol patients developed ventricular fibrillation (VF) in the hospital. The corresponding figures for atrial fibrillation or flutter were 3% (n = 87) and 3.3% (n = 94). After randomization, there was no significant difference in the number of patients who developed VF in the placebo (n = 52) and the metoprolol (n = 48) groups. The total number of episodes of VF tended to be fewer in the metoprolol group (n = 67) compared with the placebo group (n = 96). The tendency was, however, not apparent until after 5 days. When the occurrence of VF was related to high- and low-mortality risk groups, any beneficial effect of metoprolol was confined mainly to the high-risk group. A similar proportion of patients underwent electric conversion for ventricular tachyarrhythmia in the 2 groups. Although antiarrhythmic drugs were intended to be given only for major ventricular tachyarrhythmias a large proportion of patients received such treatment. Significantly more patients were treated with antiarrhythmics in the placebo (21.5%) than in the metoprolol group (19.2%, p = 0.03) during the study period, but predominantly during the first 5 days. Atrial fibrillation or flutter and other supraventricular tachyarrhythmias were significantly less frequent in the metoprolol than in the placebo group, as was the use of cardiac glycosides.

  • 33.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Development of myocardial infarction. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 23-26Article in journal (Refereed)
    Abstract [en]

    The effect of metoprolol on the development of an acute myocardial infarction (AMI) during days 0 to 3 and on late first and recurrent infarctions during days 4 to 15 has been investigated. Signs on electrocardiogram (ECG) were well balanced between the treatment groups at entry; 70% of patients had signs of suspected AMI and 19% of patients had normal ECGs. The remaining patients had abnormal ECGs but actual infarction could not be localized. The localization of suspected AMI was equivalently distributed in the 2 groups before randomization. Metoprolol altered the distribution of patients diagnosed during days 0 to 3 as having definite, possible or no AMI (p less than 0.02). In the placebo group, there were more patients with definite AMI (72.5% vs 70.5%) and less with possible AMI (5.6% vs 7.4) than in the metoprolol group. A larger proportion of patients developed a Q-wave infarction during days 0 to 3 in the placebo group (53.9%) compared with the metoprolol group (50.9%, p = 0.024). No difference in the effect of metoprolol regarding localization of the early AMI was observed. Late first myocardial infarction development (days 4 to 15) was observed in 20 patients (0.7%) in each group. Recurrent myocardial infarction tended to develop more frequently during days 4 to 15 in the placebo group compared with the metoprolol group (3.9% vs 3.0%, p = 0.08).

  • 34.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Enzymatic estimation of infarct size. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 27-29Article in journal (Refereed)
    Abstract [en]

    The maximum serum activity for aspartate aminotransferase (s-ASAT) during the first 3 days was recorded in 5,507 patients with suspected or definite acute myocardial infarction. The s-ASAT activity was corrected for the normal range from each center. The median s-ASAT activity was 4.9 arbitrary units in the placebo group versus 4.6 arbitrary units in the metoprolol group (p = 0.072). Univariate analyses indicated that the delay time between onset of symptoms and randomization and sympathetic activity at entry significantly influenced the effect of metoprolol. A similar decrease in serum enzyme activity after metoprolol treatment was observed independent of signs of infarct localization on the entry electrocardiogram.

  • 35.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Mortality. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 15-22Article in journal (Refereed)
    Abstract [en]

    After 15 days there were 142 deaths in the placebo group (4.9%) and 123 deaths in the metoprolol group (4.3%), a difference of 13% (p = 0.29). The 95% confidence limits for the relative effect of metoprolol ranged from an 8% excess (-8%) to a 33% reduction (+33%) in mortality. There was generally a lower mortality rate for metoprolol-treated patients in most subgroups and a consistent tendency for a more pronounced difference between the treatment groups in those subgroups with a placebo mortality rate higher than the average for all placebo patients. Most deaths were cardiac and occurred among patients who developed a definite myocardial infarction (97%) and most of these had a Q-wave infarction (83%). Using a simple model, the placebo mortality was found to increase with increasing number of 8 risk predictors defined from prestudy experience, from 0% in patients with no risk predictors to 11.6% in patients with any 5 or more of these risk factors. Similarly, there was an increase in the difference between the treatment groups in favor of metoprolol with increasing number of placebo risk factors. Metoprolol had no apparent effect in a low-mortality risk group (less than or equal to 2 risk factors), but there was a difference in mortality of 29% in favor of metoprolol in a high-risk group (greater than or equal to 3 risk factors) comprising one-third of the trial population.

  • 36.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Narcotic analgesics and other antianginal drugs. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 30-34Article in journal (Refereed)
    Abstract [en]

    The effect of metoprolol on chest pain has been assessed in terms of the duration and the use of narcotic analgesics, nitrates and calcium-channel blockers. Fewer metoprolol-treated patients in the MIAMI trial were given narcotic analgesics (49% of the placebo patients vs 44% of the metoprolol patients, p less than 0.001), nitrates (55% vs 53%, p = 0.10) and calcium-channel blockers (12% vs 9%, p less than 0.001). A total number of 6,697 dose equivalents of narcotic analgesics were given to the placebo group compared with 5,493 dose equivalents to the metoprolol group, a difference of 18% (p less than 0.001). Mean dose equivalents were 2.3 and 1.9, respectively. The analysis of the total use of the 3 types of treatment for ischemic chest pain showed a significantly less frequent use of treatment for chest pain in the metoprolol group than in the placebo group (p less than 0.004). The relative difference in the incidence of drug treatment tended to be more striking for patients with maximal therapy, i.e., receiving high doses of narcotic analgesics, nitrates and calcium-channel blockers. There were 22% fewer patients receiving 4 or more doses of narcotic analgesics in the metoprolol group than in the placebo group. A multivariate analysis disclosed that site of suspected infarction, delay time, entry systolic blood pressure and metoprolol treatment all had a significant effect on the use of narcotic analgesics. There was a nonsignificant tendency for heart rate to be of importance. In the placebo group the use of narcotic analgesics increased with decreasing delay time and increasing systolic blood pressure.

  • 37.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Other clinical findings and tolerability. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 39-46Article in journal (Refereed)
    Abstract [en]

    Fifteen minutes after injection there was a fall in mean heart rate (18%, p less than 0.001), systolic blood pressure (10%, p less than 0.001) and rate-pressure product (27%, p less than 0.0001) in the metoprolol group of patients in the MIAMI trial. Hypotension and bradycardia not necessarily associated with withdrawal of drug were more common in the metoprolol group (p less than 0.001). Atrioventricular block I was more common in the metoprolol group (p less than 0.03), whereas no such difference was observed for atrioventricular block II and III, asystole or pacemaker implantations. Left ventricular failure was observed no more often in the metoprolol group. The occurrence of cardiogenic shock also did not differ between the groups. Cardiac glycosides were used more in the placebo group, but diuretic and furosemide usage did not differ. For all patients mean furosemide doses and number of diuretic injections were similar in both treatment groups. Atropine (4.1 vs 6.4%) and sympathomimetic (3.2 vs 4.6%) agents were used more often in the metoprolol group during days 0 to 5 (p less than 0.05). The trial medication was withdrawn temporarily more often in the metoprolol than in the placebo group (p less than 0.001). However, permanent withdrawal of trial medication occurred with a similar frequency overall in both groups. More patients were withdrawn from the study because of cardiovascular reasons in the metoprolol group (9%) than in the placebo group (5%, p less than 0.001).

  • 38.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Patient population. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 10-14Article in journal (Refereed)
    Abstract [en]

    During the recruitment phase of the MIAMI trial (December 1982 to March 1984), data on 26,439 patients eligible for inclusion were entered. Of these, 5,778 patients were included. Current treatment with either beta blockers or calcium-channel blockers (51%) was the most predominant reason for exclusion. The randomized and excluded patients differed. The randomized patients were younger and more often men. The mean age of the patients was 59 years in both the placebo and the metoprolol groups. The 2 groups were evenly balanced with regard to basic demographic variables. The median delay between onset of symptoms and randomization was 7 hours, and 25% of the patients were included within 4 hours. Previous clinical history and pharmacologic treatment given before admission were well balanced in the groups. Mean heart rate for the 2 groups before randomization was 83 beats/min and systolic blood pressure was 141 mm Hg. Approximately 15% of randomized patients presented with pulmonary rales. Before randomization 20% of the patients had normal electrocardiograms; 70% could be classified as having electrocardiographic signs of acute myocardial infarction; and 10% presented with other electrocardiographic abnormalities. Electrocardiographic signs at entry suggested a predominance of anterior wall infarctions. The randomized patients were not representative of eligible patients and the treatment groups were well balanced at entry.

  • 39.
    Herlitz, Johan
    [external].
    Metoprolol in acute myocardial infarction. Patients and methods. The MIAMI Trial Research Group1985In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 56, no 14, p. 3-9Article in journal (Refereed)
    Abstract [en]

    The effects of early intervention with metoprolol in patients with suspected or definite acute myocardial infarction (AMI) have been assessed in a randomized, double-blind, placebo-controlled international study. Patients aged 75 years or younger were eligible for entry if they presented to a coronary care unit within 24 hours of the onset of symptoms of an AMI. Exclusion criteria included current treatment with a beta blocker or calcium-channel blocker, heart rate less than or equal to 65 beats/min, systolic blood pressure less than or equal to 105 mm Hg, contraindications and other administrative reasons. Treatment began with an intravenous loading dose (3 X 5 mg injections of metoprolol or placebo at 2-minute intervals) followed by an oral regime of 200-mg metoprolol daily or placebo. The study period was 15 days in addition to the day of randomization. The patients' clinical history and status at entry were documented. The following outcome variables were recorded: mortality, development of AMI, serum enzyme activity, electrocardiographic signs of AMI, late or recurrent AMI, arrhythmias, treatment of chest pain, concomitant treatment, adverse events and details of treatment with trial medication.

  • 40.
    Herlitz, Johan
    [external].
    Rationale, design, and organisation of the metoprolol CR/XL randomized trial in heart failure (MERIT-HF)1997In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 80, no 9B, p. 54-58Article in journal (Other academic)
    Abstract [en]

    Metoprolol is a cardioselective beta blocker that has been shown to improve left ventricular function and symptoms of congestive heart failure (CHF) and also to decrease the number of hospitalizations due to CHF. However, the effects of metoprolol on mortality in patients with CHF have yet to be determined. Accordingly, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) has been designed to investigate the effect of once-daily dosing of metoprolol succinate controlled release/extended release (CR/XL) when added to standard therapy in patients with CHF. A total of 3,200 patients will be recruited for this international, double-blind, randomized, placebo-controlled survival study. The 2 primary objectives of MERIT-HF are to determine the effect of metoprolol CR/XL on (1) total mortality and (2) the combined endpoint of all-cause mortality and all-cause hospitalizations (time to first event). Eligible patients are 40-80 years old, with a reduced left ventricular ejection fraction (< or =0.40) and symptoms of CHF (New York Heart Association functional classes II-IV). After a 2-week placebo run-in period, an optimal allocation procedure will be used to randomize patients in a 1:1 ratio to metoprolol CR/XL or matching placebo. After an initial titration phase starting with 12.5 mg or 25 mg once daily (depending on functional class), the target dose will be 200 mg in all patients who tolerate this dose. The mean follow-up is estimated to be 2.4 years. The study data will be analyzed on an intention-to-treat basis. An Independent Safety Committee will monitor the safety aspects of the trial, and an Independent Endpoint Committee will classify all endpoints.

  • 41.
    Herlitz, Johan
    [external].
    Very early trombolytic therapy in suspected acute myocardial infarction1990In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 65, no 7, p. 401-407Article in journal (Refereed)
    Abstract [en]

    Three hundred fifty-two patients with suspected acute myocardial infarction (AMI) were randomized to placebo (175) or tissue-type plasminogen activator (rt-PA) (177). Patients were eligible if evaluated within 165 minutes from onset of chest pain and if age was <75 years. Electrocardiographic criteria were not required. A mobile coronary care unit with a cardiologist present was used to initiate treatment at home in 29% of the patients. Primary endpoints were infarct size (serum lactate dehydrogenase isoenzyme1 activity), left ventricular function (radioangiography) and exercise capacity at 30 days. AMI was diagnosed in 59% of all randomized patients. The incidence was similar in the 2 groups (placebo, 108, rt-PA, 101). Among all randomized patients, rt-PA was associated with significantly decreased infarct size and an increased ejection fraction. Among rt-PA-treated patients there were significantly fewer Q-wave infarctions. No difference in exercise capacity could be detected. No benefit was found in subgroups of patients without ST-segment elevation on the initial electrocardiogram. There were 18 (10.3%) and 11 (6.2%) deaths (p = 0.23) within 30 days in the placebo and rt-PA groups, respectively. Adverse reactions were similar in both groups with no excess of complications in the home-treated group. Very early treatment with rt-PA in patients with a strong suspicion of AMI and ST-segment elevation limits infarct size and improves left ventricular function. The infarct pattern is shifted from Q-wave to non-Q-wave infarcts by rt-PA. The study suggests that thrombolysis can be given before hospital admission without additional risk. Furthermore, etectrocardiographic records are useful for selection of patients.

  • 42.
    Herlitz, Johan
    et al.
    [external].
    Edwardsson, N
    Holmberg, S
    Rydén, L
    Waagstein, F
    Waldenström, A
    Swedberg, K
    Hjalmarson, Å
    Göteborg Metoprolol Trial: effects on arrhythmias1984In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 53, no 13, p. 27-31Article in journal (Refereed)
    Abstract [en]

    During the initial hospitalization, ventricular fibrillation (VF) developed in 6 metoprolol-treated patients (0.9%) vs 17 placebo-treated patients (2.4%) after inclusion in the study (p = 0.035). There were 6 episodes of VF in the metoprolol group compared with 41 episodes in the placebo group (p less than 0.001). During the same period, 14 metoprolol-treated patients had treated ventricular tachycardia vs 26 placebo-treated patients (p = 0.076). Similar favorable results were found when the incidence of severe ventricular arrhythmias during the first rehospitalization within the 3-month double-blind treatment period was analyzed.

  • 43.
    Herlitz, Johan
    et al.
    [external].
    Ejdebäck, J
    Swedberg, K
    Waagstein, F
    Hjalmarson, Å
    Göteborg Metoprolol Trial: electrocardiographically estimated infarct size1984In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 53, no 13, p. 22-26Article in journal (Refereed)
    Abstract [en]

    In 236 patients with anterior myocardial infarction (MI), infarct size was estimated by analyzing the R- and Q-wave amplitude in 24 precordial leads 4 days after randomization. In 254 patients with inferior MI, the final R- and Q-wave amplitude was evaluated in leads II, III and aVF. Electrocardiographic signs of a smaller MI were observed in anterior MI in the metoprolol group compared with the placebo group when treatment was started 12 hours or less after the onset of pain, but no difference was found when treatment was started later. There was no sign of an effect of metoprolol in inferior MI. An immediate reduction in ST-segment elevation was observed after metoprolol treatment regardless of infarct localization or delay between the onset of pain and treatment.

  • 44.
    Herlitz, Johan
    et al.
    [external].
    Elmfeldt, D
    Hjalmarson, Å
    Holmberg, S
    Málek, I
    Nyberg, G
    Rydén, L
    Swedberg, K
    Vedin, A
    Waagstein, F
    Waldenström, A
    Waldenström, J
    Wedel, H
    Wilhelmsen, L
    Wilhelmsson, C
    Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction1983In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 51, no 8, p. 1282-1288Article in journal (Refereed)
    Abstract [en]

    In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 ± 0.5 μkat · liter−1)when the patient was treated within 12 hours of the onset of pain (13.3 ± 0.6 μkat · liter−1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol ≤12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started 12 hours and >12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve longterm prognosis.

  • 45.
    Herlitz, Johan
    et al.
    [external].
    Elmfeldt, D
    Holmberg, S
    Málek, I
    Nyberg, G
    Pennert, K
    Rydén, L
    Swedberg, K
    Vedin, A
    Waagstein, F
    Waldenström, A
    Waldenström, J
    Wedel, H
    Wilhelmsen, L
    Wilhelmsson, C
    Hjalmarson, Å
    Göteborg Metoprolol Trial: mortality and causes of death1984In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 53, no 13, p. 9-14Article in journal (Refereed)
    Abstract [en]

    During the 3-month blind treatment period there were 40 deaths in the metoprolol group compared with 62 deaths in the placebo group (p = 0.024). During the first year (after 3 months the 2 groups were treated similarly) there were 64 deaths in the metoprolol group vs 93 in the placebo group (p = 0.017) and during 2 years 92 patients died in the metoprolol group vs 120 in the placebo group (p = 0.043). The relative incidence of different causes of death did not differ significantly between the 2 treatment groups, indicating that metoprolol reduced all causes of death to the same extent as its effect on overall mortality.

  • 46.
    Herlitz, Johan
    et al.
    [external].
    Emanuelsson, H
    Swedberg, K
    Vedin, A
    Waldenström, A
    Waldenström, J
    Hjalmarson, Å
    Göteborg Metoprolol Trial: enzyme-estimated infarct size1984In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 53, no 13, p. 15-21Article in journal (Refereed)
    Abstract [en]

    In 1,375 patients serum activity of heat-stable lactate dehydrogenase (LD; E.C.1.1.1.27.) was analyzed every twelfth hour for 48 to 108 hours. The mean maximum LD activity was 11.1 +/- 0.4 mu kat X 1(-1) in the metoprolol group vs 12.4 +/- 0.5 mu kat X 1(-1) in the placebo group (p = 0.054). In patients in whom treatment was started 12 hours or less after the onset of pain, a 17% reduction in LD activity was observed (p = 0.009) and similar results were found in patients randomized 8 hours or less. Groups in which the effect after metoprolol treatment was more pronounced were those with an initially higher heart rate and also those with anterior myocardial infarction.

  • 47.
    Herlitz, Johan
    et al.
    [external].
    Hartford, M
    Aune, S
    Karlsson, T
    Occurence of hypotension during streptokinase infusion in suspected acute myocardial infarction, and its relation to prognosis and to metoprolol therapy1993In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 71, no 12, p. 1021-1024Article in journal (Refereed)
    Abstract [en]

    In all patients who received streptokinase infusion for strongly suspected acute myocardial infarction in 1 hospital during 1989 to 1990, the occurrence of hypotension during infusion is described and related to prognosis. In 54% of patients, the β blocker metoprolol was simultaneously administered intravenously. The median systolic blood pressure (BP) before infusion was 135 mm Hg, and the median value for the lowest systolic BP recorded during infusion was 100 mm Hg (p < 0.001). A positive correlation between systolic BP before streptokinase and the lowest systolic BP during infusion was found (r = 0.53; p < 0.001). Among patients administered streptokinase and metoprolol, 23% had systolic BP < 90 mm Hg, and 12% had <80 mm Hg at any time during infusion; corresponding values for patients administered streptokinase only were 47 and 30%, respectively. Patients with the lowest systolic BP < 80 mm Hg during infusion had a mortality during the first 2 weeks of 22 vs 11% for those with between 80 and 100 mm Hg, and 8% for those with >100 mm Hg (p < 0.001). However, in a multivariate analysis the systolic BP before infusion rather than the lowest systolic BP during infusion was independently associated with death. It is concluded that although patients with low systolic BP during streptokinase infusion have a high mortality, the level of systolic BP before infusion is more strongly associated with the outcome. Simultaneous use of intravenous β blockade does not increase the occurrence of hypotension during streptokinase infusion.

  • 48.
    Herlitz, Johan
    et al.
    [external].
    Hartford, M
    Blohm, M
    Karlsson, BW
    Ekström, L
    Risenfors, M
    Wennerblom, B
    Luepker, R
    Holmberg, S
    Effect of media campaign on delay times and ambulance use in suspected acut myocardial infarction1989In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 64, no 1, p. 90-93Article in journal (Refereed)
    Abstract [en]

    The early phase in suspected acute myocardial infarction (AMI) is particularly critical. More than 50% of deaths from coronary artery disease occur outside the hospital mainly due to ventricular fibrillation.1 Recent experiences strongly indicate that early intervention with thrombolysis2–4 and β blockers5,6 can limit myocardial damage and thereby improve prognosis. Delay times in suspected AMI have remained stable over the years. Therefore, a media campaign was started in the urban area of Göteborg, Sweden, with the intention to shorten delay times and to increase ambulance use in patients with suspected AMI.

  • 49.
    Herlitz, Johan
    et al.
    [external].
    Hartford, M
    Pennert, K
    Swedberg, K
    Waagstein, F
    Waldenström, A
    Wedel, H
    Wilhelmsson, C
    Hjalmarson, Å
    Goteborg Metoprolol Trial: clinical observations1984In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 53, no 13, p. 37-45Article in journal (Refereed)
    Abstract [en]

    Heart rate, systolic blood pressure and rate-pressure product were analyzed during the first 18 hours and 4 days after intravenous metoprolol or placebo. On injection of metoprolol there was an immediate decrease in mean heart rate from 72.9 0.6 to 62.7 0.4 beats/min, but no change was found in the placebo group. The difference in heart rate remained during the first 4 days. Systolic blood pressure was reduced from 144.1 0.9 to 134.6 0.9 mm Hg after intravenous metoprolol and was lower than that in the placebo group during 4 days of follow-up. Indirect signs of congestive heart failure tended to be less severe in patients given metoprolol within 12 hours of the onset of symptoms than in those given placebo. The duration of hospitalization also tended to be shorter in patients given early metoprolol treatment than in those given placebo early.

  • 50.
    Herlitz, Johan
    et al.
    [external].
    Holmberg, S
    Pennert, K
    Swedberg, K
    Vedin, A
    Waagstein, F
    Waldenström, A
    Waldenström, J
    Wedel, H
    Wilhelmsen, L
    Wilhelmsson, C
    Hjalmarsson, Å
    Göteborg Metoprolol Trial: design, patient characteristics and conduct1984In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 53, no 13, p. 3D-8DArticle in journal (Refereed)
    Abstract [en]

    The Göteborg Metoprolol Trial was a double-blind, placebo-controlled, stratified trial aimed at evaluating the effect of the beta 1-selective blocker, metoprolol, in suspected acute myocardial infarction and during 2 years of follow-up. The primary end-point was 3-month mortality (blind treatment period). Secondary end-points were 2-year mortality, indirect signs of infarct size, chest pain, arrhythmias and tolerability. The entry criteria were fulfilled in 2,802 patients, 1,395 of whom were included in the trial. Treatment started as soon as possible after arrival in hospital with intravenous administration followed by oral treatment for 3 months. All patients were randomized 48 hours or less after estimated onset of infarction and 69% were randomized at 12 hours or less. The blind treatment had to be withdrawn in 19% of all randomized patients before the end of the 3-month follow-up.

123 1 - 50 of 112
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