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Cost–Effectiveness of Clopidogrel Plus Aspirin for Stroke Prevention in Patients With Atrial Fibrillation in Whom Warfarin Is Unsuitable

Published:January 05, 2012DOI:https://doi.org/10.1016/j.amjcard.2011.11.034
      Guidelines for atrial fibrillation (AF) recommend clopidogrel plus aspirin as an alternative stroke prevention strategy in patients in whom warfarin is unsuitable. A Markov model was conducted from a Medicare prospective using data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events–A (ACTIVE-A) trial and other published studies. Base-case analysis evaluated patients 65 years old with AF, a CHADS2 (congestive heart failure, 1 point; hypertension defined as blood pressure consistently >140/90 mm Hg or antihypertension medication, 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ishemic attack, 2 points) score of 2, and a lower risk for major bleeding. Patients received clopidogrel 75 mg/day plus aspirin or aspirin alone. Patients were followed for up to 35 years. Outcomes included quality-adjusted life-years (QALYs), costs (in 2011 American dollars), and incremental cost–effectiveness ratios. Quality-adjusted life expectancy and costs were 9.37 QALYs and $88,751 with clopidogrel plus aspirin and 9.01 QALYs and $79,057 with aspirin alone. Incremental cost–effectiveness ratio for clopidogrel plus aspirin was $26,928/QALY. With 1-way sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY, clopidogrel plus aspirin was no longer cost effective when the CHADS2 score was ≤1, major bleeding risk with aspirin was ≥2.50%/patient-year, the relative risk decrease for ischemic stroke with clopidogrel plus aspirin versus aspirin alone was <25%, and the utility of being healthy with AF on combination therapy decreased to 0.95. Monte Carlo simulation demonstrated that clopidogrel plus aspirin was cost effective in 55% and 73% of 10,000 iterations assuming willingness-to-pay thresholds of $50,000 and $100,000/QALY. In conclusion, clopidogrel plus aspirin appears cost-effective compared to aspirin alone for stroke prevention in patients with AF with a CHADS2 of ≥2 and a lower risk of bleeding.
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      Linked Article

      • Clopidogrel in Atrial Fibrillation: Is There Any Justification Now in the Era of New Anticoagulants?
        American Journal of CardiologyVol. 110Issue 1
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          I read with interest the report regarding the combination of aspirin and clopidogrel versus aspirin alone for stroke prevention in those deemed unsuitable for warfarin therapy.1 As the investigators point out, there was modest stroke reduction (relative risk reduction 28%) in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events–Aspirin (ACTIVE-A) trial, but at the cost of increased bleeding.2 This study was the basis for their cost-effectiveness analysis. However, the Apixaban Versus Acetylsalicylic Acid to Prevent Strokes (AVERROES) investigators recently demonstrated much more impressive reductions in stroke (relative risk reduction >50%) with the oral factor Xa inhibitor apixaban, compared to aspirin, in patients with atrial fibrillation deemed unsuitable for warfarin therapy.
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