Dual Antiplatelet Therapy Strikes Out in AFib

Summary and Comment |
July 19, 2006

Dual Antiplatelet Therapy Strikes Out in AFib

  1. Beat J. Meyer, MD

Warfarin remains the standard of care for preventing stroke in patients with atrial fibrillation.

  1. Beat J. Meyer, MD

Oral anticoagulation therapy is the standard for preventing stroke in patients with atrial fibrillation (AF). Aspirin, the alternative for warfarin-ineligible AF patients, is less effective than warfarin for stroke prevention (JAMA 2002; 288:2441). In a new, industry-sponsored trial, researchers randomized 6706 AF patients (mean age, 70; 66% men) with at least one stroke risk factor to receive dual antiplatelet therapy — clopidogrel (75 mg/day) plus aspirin (75–100 mg/day) — or oral anticoagulation therapy, usually warfarin (target INR, 2–3). Baseline use of other medications (ACE inhibitors in 54%, ARBs in 15%, beta-blockers in 57%, digoxin in 37%, and statins in 38%) was similar in the two groups. The primary endpoint was the first incident stroke, non-CNS systemic embolism, MI, or vascular death.

The study was stopped early, at a median follow-up of 1.3 years, because oral anticoagulation was clearly better than clopidogrel plus aspirin, as shown by annual incidences of the primary endpoint (3.9% vs. 5.6%; P<0.0003) and any stroke (1.4% vs. 2.4%; P<0.001). Major bleeding incidence was similar in the two groups (2.2%–2.4%), but oral anticoagulation was associated with significantly more hemorrhagic strokes (0.36% vs. 0.12%) and fewer minor bleeds (11.5% vs. 13.6%).

Comment

The efficacy of long-term dual antiplatelet therapy was disappointing in this trial, as was the on-treatment incidence of major bleeding. Although the findings are limited by lower-than-expected rates of events overall and of stroke specifically, warfarin remains the gold standard for preventing stroke in AF patients at increased risk for embolic events. Still, the search for safer options must continue.

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