AIM: Dual-antiplatelet therapy may work; anticoagulants may be better
Combining clopidogrel and aspirin in patients who could not tolerate warfarin showed benefit, according to a study published Nov. 1 in Annals of Internal Medicine. However, the researchers said that they could not rule out the fact that this combination could have either no benefit or a very small harm in some patients. An editorialist added that as more novel anticoagulants get approved, the drug class may outshine dual-antiplatelet therapy.

“Adding clopidogrel to aspirin therapy reduces stroke in patients with atrial fibrillation (AF) but increases hemorrhage,” Stuart J. Connolly, MD, of the McMaster University in Hamilton, Ontario, and colleagues wrote.

To better understand this benefit, Connolly and colleagues performed an observational cohort study of the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) clinical trial to evaluate the net benefit of dual-antiplatelet therapy.

The study included 10,041 AF patients, 7,554 of whom were not candidates for warfarin. The study’s primary endpoint was ischemic and hemorrhagic events.

Results showed that adding clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi Aventis) to aspirin therapy prevented 0.57 ischemic stroke equivalents per 100 patient-years of treatment when weighted by hazard for death after ischemia or hemorrhaging events and 0.67 ischemic stroke equivalents when weighted by death or disability after ischemic or hemorrhaging events.

In an accompanying editorial, Margaret C. Fang, MD, MPH, of the University of California, San Francisco, questioned the optimal therapy for the prevention of stroke in AF patients, whose risk for ischemic stroke is increased nearly five-fold.

While anticoagulation therapy with vitamin K antagonists, like warfarin, has been shown to reduce AF-related ischemic stroke events, it has also been shown to increase the risk of bleeding. Additionally, warfarin patients must undergo frequent INR checks.

“Selecting the most appropriate antithrombotic therapy for a patient is one of the most important management decisions in atrial fibrillation, and the net clinical benefit associated with a given therapeutic choice should guide this decision,” Fang wrote.

Fang argued that the new wave of oral anticoagulants introduced to the market has “overshadowed” dual-antiplatelet therapy. However, Fang offered that these direct thrombin inhibitors and factor Xa inhibitors tend to be at least as effective and safe as warfarin and are administered with a fixed-dose.

“As newer anticoagulants become available, the role of dual-antiplatelet therapy in atrial fibrillation may become even more limited,” Fang noted. “Although dual-antiplatelet therapy has not yet been directly compared with newer anticoagulants, it is unlikely (extrapolating from the comparisons with warfarin) to be as effective as these agents.”

Fang offered that in the future, because of the boom of other anticoagulants on the market, dual-antiplatelet therapy might only now be considered for patients at a high-risk for stroke who cannot receive anticoagulants.

“The optimal antithrombotic therapy should be selected in the context of the evolving field of stroke prediction in atrial fibrillation,” Fang concluded. “[F]uture interventions could obviate the need for antithrombotic therapy in atrial fibrillation entirely.”