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Anticoagulants for stroke prevention in atrial fibrillation: what is the right rate and where do we go from here?

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 226–227 (2005)Cite this article

Atrial fibrillation (AF) is the most clinically significant arrhythmia among adults.1 It affects millions of people worldwide and increases the risk of ischemic stroke fivefold.2 Aggressive research efforts to reduce the incidence of AF-related stroke have focused primarily on the evaluation of two antithrombotic therapies: the oral vitamin K antagonist, warfarin (and other coumarins), and the antiplatelet agent, aspirin. Randomized trials have proven the efficacy of adjusted-dose warfarin, targeted to an international normalized ratio (INR) range 2.0–3.0, for stroke prevention in AF. Warfarin decreases the relative risk of stroke by 68% compared with control3 and by 52% compared with aspirin,4 although combining warfarin with aspirin increases the bleeding risk. Thus controversy surrounds the effectiveness of adding aspirin to adjusted-dose warfarin in selected patient subgroups. In certain clinical settings, warfarin is highly effective and adequately safe in patients with AF,5 and US and international guidelines currently recommend warfarin for the large majority of patients with AF.

Given the dramatic efficacy of warfarin, why is it not given to everyone with AF? Unfortunately, warfarin is a narrow therapeutic index drug affected by numerous factors. For AF, the optimal anticoagulation intensity appears to be an INR between 2.0 and 3.0, which maximizes the benefit for stroke prevention and only moderately increases bleeding risk. A lower INR does not prevent stroke and a high INR, especially above 4.0, markedly increases the risk of bleeding. Even in carefully monitored trial settings, however, the amount of time spent in the therapeutic INR range is only 60–68%. Factors contributing to this variability include host factors, such as genetic variation in warfarin metabolism, vitamin K and alcohol intake, and interactions with many prescription and over-the-counter medications. Warfarin therapy is also burdensome to patients and providers because of the need for frequent INR monitoring. The challenges faced in efficiently delivering warfarin therapy and achieving optimal INR levels across populations with AF are formidable.

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Authors and Affiliations

  1. Kaiser Permanente of Northern California, Oakland, CA, USA

    Alan S Go

  2. Departments of Epidemiology, Biostatistics, and Medicine, at the University of California, San Francisco, CA, USA

    Alan S Go

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  1. Alan S Go
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Correspondence to Alan S Go.

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Go, A. Anticoagulants for stroke prevention in atrial fibrillation: what is the right rate and where do we go from here?. Nat Rev Cardiol 2, 226–227 (2005). https://doi.org/10.1038/ncpcardio0198

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