OBJECTIVES: Clopidogrel’s effectiveness is reduced significantly for secondary prevention of thrombotic events after acute coronary syndrome (ACS) in patients with CYP2C19*2 mutations. Ticagrelor, a novel antiplatelet agent, does not require activation by the CYP2C19 enzyme and was superior to clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor. We aim to determine the cost-effectiveness of genotype-driven treatment, in which ticagrelor is prescribed in the presence of CYP2C19*2 mutations and clopidogrel in their absence, compared to prescribing ticagrelor universally. METHODS: A hybrid decision tree/Markov model was used to derive 30-year medical costs (in 2009 US$) and outcomes for a cohort of Medicare ACS patients of age 65 receiving either a genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the PLATO study. Mortality and repeat myocardial infarction risk were estimated using Medicare inpatient claims of ACS patients. Costs and quality adjustments were derived from literature reviews.RESULTS: Over a 30-year period the incremental cost-effectiveness ratio (ICER) for universal ticagrelor was $8,827 per QALY compared to genotype-driven treatment. Universal ticagrelor and genotype-driven treatment had respective per capita costs of $10,096 and $8,868. Universal ticagrelor resulted in 0.14 QALYs gained per person relative to genotype-driven treatment. The ICER was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel and remained below $50,000 per QALY until a monthly price of $737 for ticagrelor or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, the ICER was below $50,000 per QALY in 97.4% of simulations. CONCLUSIONS: Prescribing ticagrelor universally increases quality-adjusted life expectancy for ACS patients at a cost below typically accepted thresholds.