Oral Anticoagulation Remains Treatment of Choice in AF
By Wayne Kuznar
Dallas—Oral anticoagulant therapy is superior to the combination of clopidogrel (Plavix) and aspirin in preventing adverse vascular outcomes in patients with arterial fibrillation (AF). The 2 treatment regimens were compared in a study of >6500 patients, the results of which were reported at the American Heart Association’s Scientific Sessions 2005.
“We found an advantage to oral anticoagulation if an optimal INR [International Normalized Ratio] is maintained,” said Stuart J. Connolly, MD, director, Division of Cardiology, McMaster University, Hamilton, Ontario, Canada.
The study included 6706 patients with AF and at least 1 additional stroke factor. They were randomly assigned to standard care with oral anticoagulant therapy, usually warfarin (Coumadin) at a dosage to maintain an INR of 2.0 to 3.0, or antiplatelet therapy with clopidogrel, 75 mg/day, and aspirin, 75 to 100 mg/day.
At the time of enrollment, more than three fourths of the patients assigned to either treatment had previous exposure to oral anticoagulant therapy. “This was more of a trial of switching therapies rather than de novo treatment,” said Dr Connolly.
The trial was designed to show noninferiority of the clopidogrel/aspirin regimen compared with the oral anticoagulant regimen.
The trial was halted early after the study’s Data Safety and 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 3.93% in the patients assigned to oral anticoagulation compared with 5.64% in those assigned to the antiplatelet regimen, representing a 47% reduction (P = .002) in the anticoagulant group compared with the clopidogrel-aspirin group.
Rates of bleeding were similar overall in the 2 groups; the investigators had expected a lower rate of bleeding in the antiplatelet group. The treatment effects, however, were different between patients who had been taking warfarin at baseline and those who were not, especially related to bleeding risk. Patients randomized to clopidogrel-aspirin had a 36% excess risk of major bleeding if they had previous exposure to warfarin, whereas among the patients without previous warfarin exposure, the risk of a major bleed was 37% lower in the clopidogrel-aspirin group compared with the oral anticoagulation group.
For patients receiving 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, no significant difference occurred in study drug discontinuation between the 2 treatment groups among patients who had previous 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 previous experience with oral anticoagulation, said Dr Connolly.
He noted that control of INR was poorer in those patients randomized to oral anticoagulation who were not on it at study entry. “Good control of INR is important to determining the effects of oral anticoagulation and clopidogrel/aspirin,” he said. “There was little benefit [to oral anticoagulation] in centers where INR control was not maintained.”
Jonathan Halperin, MD, of Mount Sinai Medical Center, New York City, said that maintaining an INR in the normal range is “no easy feat”; nevertheless, the results of the study were convincing in favor of warfarin over antiplatelet therapy. Previous studies have shown a 30% to 40% reduction in stroke risk with oral anticoagulation when it has been compared with antiplatelet therapy, much like Dr Connolly’s study, he said.