Oral Anticoagulation for Stroke Prevention in Patients with Atrial Fibrillation

Abstract & Commentary

By Matthew E. Fink, MD, Vice Chairman, Professor of Clinical Neurology, Weill Cornell Medical College; Chief, Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital. Dr. Fink reports no financial relationship relevant to this field of study.

Synopsis: Warfarin remains superior to antiplatelet agents for stroke prevention in patients with atrial fibrillation.

Source: Connolly S, et al. Clopidogrel Plus Aspirin versus Oral Anticoagulation for Atrial Fibrillation in the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W): A Randomized Controlled Trial. Lancet. 2006;367:1903-1912.

In the 1980s, primarily from the Framingham Study, atrial fibrillation (AF) was a clearly established major risk factor for stroke and other cardioembolic vascular events. In the 1990s, several randomized clinical trials established the efficacy of vitamin K-dependent oral anticoagulants (warfarin and other coumarins) in preventing stroke from AF, and also demonstrated its superiority over aspirin. However, because of the difficulty in managing patients who are taking oral anticoagulants (OA), and the reluctance of many patients to undergo frequent blood tests and physician visits, there is a continuing desire to find a simple and safe regimen as an alternative to OA.

Connolly and colleagues compared the effectiveness of aspirin (75-100 mg per day) plus clopidogrel (75 mg per day) versus OA with a coumarin agent. Patients were enrolled if they had AF plus one or more risk factors for stroke—age 75 years or older, treatment for hypertension, previous stroke, TIA, non-CNS embolus, decreased left ventricular ejection fraction, peripheral arterial disease, diabetes mellitus, or coronary artery disease. They were randomly allocated to receive OA (target INR, 2.0-3.0; n = 3371) or clopidogrel plus aspirin (n = 3335). Primary outcome was the first occurrence of stroke, non-CNS systemic embolism, myocardial infarction, or vascular death.

The study was stopped early because of clear evidence for superiority of OA over combined antiplatelet therapy. There were 165 primary events in the OA group (annual risk = 3.93%) and 234 in the aspirin/clopidogrel group (annual risk = 5.6%), with an increased relative risk of 1.44 (1.18-1.76; P = 0.0003). In addition, there was no significant difference in overall bleeding complication rates between the 2 groups. Patients who were already on OA therapy, and were maintained on OA, had the best overall therapeutic response, with the lowest rate of primary events, and the lowest rate of bleeding complications.


In the quest for a safer and better oral antithrombotic treatment to prevent stroke in patients with AF, warfarin and its relatives still come out on top when compared to combination therapy with aspirin and clopidogrel. It is projected that the number of people with AF will double by the year 2050 and, therefore, neurologists will be treating more patients who have stroke and TIA with some form of OA. The good news from the ACTIVE study is that the annual rate of stroke in the aspirin/clopidogrel group was 2.4%; much lower than in other studies that looked at aspirin alone. It is likely that better management of all risk factors has resulted in an overall reduction in stroke rates in patients with AF, and this finding should give us hope and optimism for the future.