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Outcome of Stroke Prevention: Analyses Based on Data from Riks-Stroke and Other Swedish National Registers
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Andreas Terént)
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to explore variations in stroke prevention and the effect of prevention on outcome. The studies were based on patients registered in the Swedish Stroke Register between 2001 and 2009 and although used to different extents in each paper, additional information was retrieved through linkage to The National Patient Register, the Cause of Death Register, the Prescribed Drug Register and the Total Population Register.

Cardiovascular risk factors were prevalent among ischemic stroke (IS) patients; however, they were not always prescribed the drugs recommended, and increasing age was an important negative predictor (Paper I).

After IS, the rate of hemorrhage in patients prescribed antiplatelet agents (2.4 per 100 person-years) was double to results from randomized controlled trails, but was similar for patients prescribed warfarin (2.5 per 100 person-years).  Age ≥75 years and previous hemorrhage were associated with a moderately increased risk of future hemorrhage (Paper II).

Among IS patients with atrial fibrillation, one-third was prescribed warfarin and two-thirds were prescribed antiplatelets. After adjustment for a propensity score (used to adjust for the non-randomized design), warfarin was associated with a reduced risk of death (0.67; 95% CI, 0.63-0.71) (Paper III). The rate of subsequent hemorrhagic stroke was 0.4 per 100 person-years and the risk did not change (HR 1.04; 95% CI, 0.73-1.48) when later years of the 2000s (inclusion period 2005-8: follow-up until 2009) was compared with earlier years (inclusion period 2001-4: follow-up until 2005) (Paper IV, cohort).

Although the risk of first-ever hemorrhagic stroke more than doubled with warfarin than without, the risk did not change between 2006 and 2009 (Paper IV, case-control).

In summary, the prescription of secondary preventive drugs varies with age, even though cardiovascular risk factors are prevalent in all ages. The risk of death and hemorrhage are affected by the type of antithrombotic prescribed. Therefore, it is important individual’s stroke and bleeding risks in stroke prevention are assessed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 52 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 757
Keyword [en]
Stroke, Epidemiology, Age groups, Risk factors, Atrial fibrillation, Secondary prevention, Anticoagulants, Antiplatelets, Hemorrhage, Mortality.
National Category
Clinical Medicine
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-171871ISBN: 978-91-554-8322-7 (print)OAI: oai:DiVA.org:uu-171871DiVA: diva2:512556
Public defence
2012-05-16, Enghoffsalen, ing 50, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-04-24 Created: 2012-03-28 Last updated: 2012-08-01Bibliographically approved
List of papers
1. Ischemic Stroke and Secondary Prevention in Clinical Practice: A Cohort Study of 14 529 Patients in the Swedish Stroke Register
Open this publication in new window or tab >>Ischemic Stroke and Secondary Prevention in Clinical Practice: A Cohort Study of 14 529 Patients in the Swedish Stroke Register
Show others...
2010 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, no 7, 1338-1342 p.Article in journal (Refereed) Published
Abstract [en]

Background and Purpose

Secondary prevention is recommended after stroke, but adherence to guidelines is unknown. We studied the prescription of antiplatelet drugs, angiotensin-converting enzyme inhibitors, statins, and anticoagulant drugs and their relation to risk of death.

Methods

Patients with first-ever ischemic stroke in 2005 were registered in the Swedish Stroke Register. Odds ratios, hazard ratios, and 95% CIs were calculated using logistic and Cox proportional hazard regression models. Adjustments were performed for age, sex, cardiovascular risk factors, other drug therapies, and activities of daily living function.

Results

In total, 14 529 patients with a mean age of 75.0 (±11.6) years were included. They were followed for 1.4 (±0.5) years: 52% had hypertension, 26% atrial fibrillation, 19% diabetes, and 15% were smokers. The odds ratio for prescription of antiplatelet was 2.20 (95% CI, 1.86 to 2.60) among the oldest patients (≥85 years of age) compared with the youngest (18 to 64 years of age). The corresponding odds ratio was 0.38 (0.32 to 0.45) for prescriptions of angiotensin-converting enzyme inhibitors, 0.09 (0.08 to 0.11) for statins, and 0.07 (0.05 to 0.09) for anticoagulant therapy. Prescription of statin and anticoagulant therapy was associated with reduced risk of death (hazard ratio, 0.78 [0.65 to 0.91] and hazard ratio, 0.58 [0.44 to 0.76], respectively) but not the prescription of antiplatelet drugs or angiotensin-converting enzyme inhibitors.

Conclusions

The prescription of antiplatelet, angiotensin-converting enzyme inhibitors, statins, and anticoagulant therapy was strongly age related. Statin and anticoagulant therapy was associated with reduced risk of death and seemed to be underused among elderly patients. These findings should encourage physicians to follow today's guidelines for stroke care.

Keyword
cerebral infarction, risk factors, secondary prevention, age groups
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135177 (URN)10.1161/STROKEAHA.110.580209 (DOI)000279272200008 ()20522818 (PubMedID)
Available from: 2010-12-06 Created: 2010-12-06 Last updated: 2017-12-12Bibliographically approved
2. Hemorrhages After Ischemic Stroke: Relation to Age and Previous Hemorrhages in a Nationwide Cohort of 58 868 Patients
Open this publication in new window or tab >>Hemorrhages After Ischemic Stroke: Relation to Age and Previous Hemorrhages in a Nationwide Cohort of 58 868 Patients
2013 (English)In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 8, no 2, 80-86 p.Article in journal (Refereed) Published
Abstract [en]

Background:

In randomized controlled trials of secondary prevention after stroke, the risk of hemorrhage varies between 1% and 5% per year in patients with antithrombotic therapy, i.e. anticoagulants and antiplatelets.

Aim:

To explore the rate and the risk of hemorrhage after stroke in a nationwide cohort.

Methods:

We identified 58 868 first-ever ischemic stroke patients in the Swedish Stroke Register during 2001 to 2005 (=index stroke) and followed them by record linkage to the National Patient Register. Rates of hemorrhage and hazard ratios, for comparisons of rates between subgroups, were calculated.

Results:

Of the 58 586 ischemic stroke patients identified, 5527 (9.4%) had a history of hemorrhage. During follow-up (mean 2.0 years), 2876 patients endured a hemorrhage, giving an average hemorrhage rate of 2.6 (95% confidence interval 2.5-2.7) per 100 person-years. After index stroke, 11% of the patients were discharged with anticoagulants, and 79% with antiplatelets. Given the differences in baseline characteristics, the hemorrhage rates (per 100 person-years) were 2.5 (95% confidence interval 2.2-2.8), 2.4 (95% confidence interval 2.3-2.5), and 3.8 (95% confidence interval 3.5-4.2) in patients prescribed anticoagulants, antiplatelets, and no antithrombotics, respectively. There was an increased risk of hemorrhage in patients ≥75 years compared to those <75 years (hazard ratio = 1.61, 95% CI 1.49-1.73), and in patients with previous hemorrhages compared to those without (hazard ratio = 1.82, 95% confidence interval 1.64-2.02).

Conclusions:

When antithrombotics were used in large-scale clinical practice, the observed rates of hemorrhage were similar with anticoagulant therapy but increased with antiplatelet therapy, compared to rates reported in randomized controlled trials. Old age and previous hemorrhage were associated with an increased risk of hemorrhage after an ischemic stroke.

Keyword
Ischemic stroke, Age Groups, Antiplatelet and anticoagulant treatment for secondary stroke prevention, Hemorrhage
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-171611 (URN)10.1111/j.1747-4949.2011.00718.x (DOI)000313880700006 ()
Available from: 2012-03-23 Created: 2012-03-23 Last updated: 2017-12-07Bibliographically approved
3. Reduced Risk of Death with Warfarin: Results of an Observational Nationwide Study of 20 442 Patients with Atrial Fibrillation and Ischemic Stroke
Open this publication in new window or tab >>Reduced Risk of Death with Warfarin: Results of an Observational Nationwide Study of 20 442 Patients with Atrial Fibrillation and Ischemic Stroke
2013 (English)In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 8, no 8, 689-695 p.Article in journal (Refereed) Published
Abstract [en]

Background

Warfarin is demonstrated to be superior in efficacy over antiplatelet agents (AP) for the prevention of stroke, but the relationship between warfarin and mortality is less clear. Our aim was to investigate this relationship in a large cohort of unselected patients with atrial fibrillation and ischemic stroke.

Methods

This observational study was based on patients who were discharged alive and registered in the Swedish Stroke Register in 2001 through 2005. Vital status was retrieved by linkage to the Swedish Cause of Death Register. We calculated a propensity score for the likelihood of warfarin prescription at discharge from hospital. The risk of death and 95% confidence intervals (CI) were estimated in Cox regression models.

Results

Out of the 20 442 patients with atrial fibrillation and ischemic stroke (mean age=79.5 years), 31% (n=6399) were prescribed warfarin. After adjustment for the propensity score, warfarin was associated with a reduced risk of death (0.67; 95% CI, 0.63-0.71). The crude rate (per 100 person-years) of fatal non-hemorrhagic stroke was lower in patients who received warfarin (1.60; 95% CI, 1.34-1.89) compared to those who received AP (6.83; 95% CI, 6.42-7.25). The rates (per 100 person-years) of fatal hemorrhagic stroke were 0.21 (95% CI, 0.12-0.32) and 0.43 (95% CI, 0.34-0.55) in patients prescribed warfarin and AP therapy, respectively.

Conclusions

In addition to its established benefit for stroke prevention, warfarin therapy in patients with atrial fibrillation and ischemic stroke was associated with a reduced risk of death, without an increased risk of fatal hemorrhagic stroke.

Keyword
Ischemic Stroke, Atrial Fibrillation, Anticoagulants, Antiplatelets, Mortality, Epidemiology
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-171626 (URN)10.1111/j.1747-4949.2012.00855.x (DOI)000327257600020 ()22928583 (PubMedID)
Available from: 2012-03-23 Created: 2012-03-23 Last updated: 2017-12-07Bibliographically approved
4. The Risk of Warfarin-Associated Hemorrhagic Stroke for the Years 2001 to 2009: An Analysis Based on 20 486 Stroke Patients in the Swedish Stroke Register
Open this publication in new window or tab >>The Risk of Warfarin-Associated Hemorrhagic Stroke for the Years 2001 to 2009: An Analysis Based on 20 486 Stroke Patients in the Swedish Stroke Register
2012 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836Article in journal (Refereed) Submitted
Keyword
Epidemiology, Stroke, Risk factors, Anticoagulants
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-171627 (URN)
Available from: 2012-03-23 Created: 2012-03-23 Last updated: 2017-12-07Bibliographically approved

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