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Reduced Risk of Death with Warfarin: Results of an Observational Nationwide Study of 20 442 Patients with Atrial Fibrillation and Ischemic Stroke
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Akut- och internmedicin, Andreas Terént)
Umeå University, Department of Statistics.
Lund University, Department of Laboratory Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Akut- och internmedicin, Andreas Terént)
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.

Place, publisher, year, edition, pages
2013. Vol. 8, no 8, 689-695 p.
Keyword [en]
Ischemic Stroke, Atrial Fibrillation, Anticoagulants, Antiplatelets, Mortality, Epidemiology
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-171626DOI: 10.1111/j.1747-4949.2012.00855.xISI: 000327257600020PubMedID: 22928583OAI: oai:DiVA.org:uu-171626DiVA: diva2:511912
Available from: 2012-03-23 Created: 2012-03-23 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Outcome of Stroke Prevention: Analyses Based on Data from Riks-Stroke and Other Swedish National Registers
Open this publication in new window or tab >>Outcome of Stroke Prevention: Analyses Based on Data from Riks-Stroke and Other Swedish National Registers
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
Stroke, Epidemiology, Age groups, Risk factors, Atrial fibrillation, Secondary prevention, Anticoagulants, Antiplatelets, Hemorrhage, Mortality.
National Category
Clinical Medicine
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-171871 (URN)978-91-554-8322-7 (ISBN)
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

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