Although the ACTIVE W arm of the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events has ended early because anticoagulation was found to be superior to antiplatelet therapy, the other two arms continue to evaluate optimal therapy for patients who cannot tolerate anticoagulation and the role of irbesartan in prevention of vascular events, according to a presentation at the annual meeting of the European Society of Cardiology.

The ACTIVE trial involves over 3,000 patients in 30 countries: The ACTIVE W arm compared standard oral anticoagulation with the antiplatelet therapy of aspirin plus clopidogrel, and this part of the program was discontinued when superior efficacy of oral anticoagulation was established.

Current clinical guidelines recommend the use of oral anticoagulant therapy for most patients with atrial fibrillation in order to avoid embolic events. However, oral anticoagulant therapy is associated with a narrow therapeutic window, requires regular monitoring, and is contraindicated in some patients. Aspirin is an option in patients who cannot tolerate oral anticoagulants. The ACTIVE trial was designed to evaluate the appropriate place of clopidogrel plus aspirin in prevention of embolic events in patients with atrial fibrillation.

Salim Yusuf, PhD, Chair of the Steering Committee for the ACTIVE trial said “In the ACTIVE W trial, most of the patients had been receiving oral anticoagulation prior to entry into the trial. These patients achieved high levels of compliance to oral anticoagulation in the recommended therapeutic range.”

Stuart Connolly, MD, principle investigator of the trial as a whole, emphasized that “it is important to continue the ACTIVE A and ACTIVE I parts of the study program to evaluate the potential role which clopidogrel can play in the management of atrial fibrillation patients who are intolerant of oral anticoagulants and to understand the role of irbesartan in patients with atrial fibrillation.”

The two ongoing arms of the phase III multinational trial are ACTIVE A and ACTIVE I. ACTIVE A compares aspirin alone with aspirin plus clopidogrel in patients with a contraindication for oral anticoagulation or who are unwilling to take oral anticoagulants.

ACTIVE I is evaluating whether the angiotensin II receptor antagonist irbesartan is superior to placebo (in addition to usual antihypertensive therapy) in preventing vascular events in patients with atrial fibrillation.