Cost-effectiveness of clopidogrel plus aspirin for stroke prevention in patients with atrial fibrillation in whom warfarin is unsuitable.

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 CHADS(2) (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 CHADS(2) 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 CHADS(2) of ≥2 and a lower risk of bleeding.