Current Trial-Associated Outcomes With Warfarin in Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation: A Meta-Analysis

Study Questions:

What are the risks and benefits of warfarin for stroke prevention in patients with atrial fibrillation (AF) in contemporary practice?


This was a meta-analysis of randomized clinical trials (RCTs) that reported the safety and efficacy of warfarin within the past 10 years. The primary efficacy outcome was ischemic or hemorrhagic stroke or systemic embolism.


The meta-analysis included eight RCTs with a total of 32,053 patients. The agents compared to warfarin consisted of ximelagatran, idraparinux, aspirin, aspirin plus clopidogrel, dabigatran, rivaroxaban, and apixaban. The percentage of time in international normalized ratio (INR) range of 2-3 varied between 55% and 68%, and was >60% in seven of the eight RCTs. The pooled event rate for stroke/systemic embolism was 1.66%/year. The incidence of major bleeding was 1.4-3.4%/year. The pooled rate of intracranial hemorrhage was 0.61%. Age ≥75 years, female gender, history of stroke, and high CHADS2 score were associated with a higher risk of stroke/embolism.


The authors concluded that the contemporary risk of stroke/systemic embolism in patients with AF treated with warfarin is 1.66%/year.


Analysis of RCTs published in 1989-1993 demonstrated a pooled incidence of stroke/systemic embolism of 2.09%/year. The contemporary risk is approximately 20% lower. The apparent reduction in risk of stroke/embolism with contemporary warfarin therapy can be attributed to two factors: 1) the time in therapeutic range typically was <60% in older RCTs and now usually is >60%; 2) the lower limit of therapeutic INR range was as low as 1.4-1.5 in the older RCTs and now uniformly is 2.0.

Clinical Topics: Anticoagulation Management, Nonstatins, Novel Agents, Statins

Keywords: Oligosaccharides, Risk, Stroke, Morpholines, Warfarin, Ticlopidine, Pyrazoles, International Normalized Ratio, Incidence, Intracranial Hemorrhages, beta-Alanine, Azetidines, Benzylamines, Benzimidazoles, Embolism, Pyridones, Risk Assessment

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