2005 AHA Scientific Sessions: ACTIVE-W

The trial, known as ACTIVE-W, for Atrial Fibrillation Clopidogrel Trial with Irebsartan for Prevention of Vascular Events, was terminated early due to a difference in efficacy in favor of warfarin, said Stuart J. Connolly, MD.

As such, oral anticoagulants remain the treatment of choice in patients with AF. However, "we found an advantage to oral anticoagulation if an optimal INR [International Normalized Ratio] is maintained," said Dr Connolly, director of the division of cardiology at McMaster University in Hamilton, Ontario, Canada.

More than three-fourths of the patients assigned to either treatment had prior exposure to oral anticoagulant therapy at the time of enrollment. "This was more of a trial of switching therapies rather than de novo treatment," Dr Connolly said.

The trial was designed to demonstrate noninferiority of the clopidogrel/aspirin regimen compared with the oral anticoagulant regimen, but the trial was halted early after the study's Data Safety Monitoring Board alerted the Steering Committee to a difference in efficacy in favor of oral anticoagulation over antiplatelet therapy.

The annual risk of achieving the primary end point of stroke, myocardial infarction, embolism, and vascular death was 47% greater (5.64% per year vs 3.93% per year; P=.0002) in the clopidogrel-aspirin group compared with the warfarin group.

The rates of bleeding were similar overall in the 2 groups. The treatment effects were different between patients who had been on warfarin at baseline and those who were not, especially as related to bleeding risk. Patients randomized to clopidogrel/aspirin had a 36% excess risk of major bleeding if they had prior exposure to warfarin (P=.027), whereas among the patients without prior warfarin exposure, the risk of a major bleed was 37% lower in the clopidogrel-aspirin group versus the oral anticoagulation group (P=.08).

For patients on oral anticoagulation at study entry, the study drug discontinuation rates were 6.0% in the patients assigned to oral anticoagulation and 13.4% in those assigned to antiplatelet therapy. However, there was no significant difference in study drug discontinuation between the 2 treatment groups in the patients who had prior exposure to warfarin.

Thus, the study may have been biased in favor of oral anticoagulation by selection of a large group of patients who had prior experience with oral anticoagulation, Dr Connolly said.

He noted that control of INR was poorer in those patients randomized to oral anticoagulation therapy who were not on the therapy at study entry.

"Good control of INR is important to determining the effects of oral anticoagulation and clopidogrel/aspirin," said Dr Connolly. "There was little benefit [to oral anticoagulation] in centers where INR control was not maintained."