ACTIVE-W—one study under the larger umbrella of the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) Trial—was discontinued in September 2005 after an excess risk of vascular events was observed in participants receiving clopidogrel plus aspirin compared with those receiving warfarin.

An increased risk of 1.7% (47% relative increase) of stroke and MI was noted in the clopidogrel/ASA arm versus the warfarin arm.

The ACTIVE trial, with 600 sites in 30 countries and more than 6,500 participants, is the largest randomized study program ever conducted to evaluate therapeutic strategies in atrial fibrillation (AF). ACTIVE has three study components, ACTIVE-A, ACTIVE-I, and ACTIVE-W. Both ACTIVE-A and ACTIVE-I are ongoing.

In announcing the halt of ACTIVE-W, Stuart Connolly, MD, director of the Division of Cardiology at McMaster University, Hamilton, Ontario, Canada, and principal investigator of ACTIVE, said that “the Data and Safety Monitoring Board alerted the ACTIVE Steering Committee to the difference in efficacy, clearly in favor of oral anticoagulants compared with the clopidogrel/aspirin arm in ACTIVE-W.”

Oral anticoagulation (OAC) remains the standard of care in preventing stroke in AF, but clinicians must also confront management concerns including frequent INR monitoring and a narrow therapeutic window. And patients at higher risk for bleeding cannot take warfarin—but the alternative, aspirin, offers limited protection against embolic events.

ACTIVE-A will assess clopidogrel + aspirin compared with aspirin alone in patients with a contraindication to OACs or who are unwilling to take an OAC. ACTIVE-I will evaluate irbesartan versus placebo (along with antihypertensive therapy) in preventing vascular events in patients with atrial fibrillation. The ongoing ACTIVE trials will offer new information and alternatives in managing the significant risk of stroke and other vascular events associated with AF.