CYP2C19: a decision analysis genotype plus platelet reactivity-guided antiplatelet therapy in acute coronary syndrome patients: a decision analysis

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Abstract

Objectives

We examined the cost-effectiveness of CYP2C19 genotype plus platelet reactivity-guided antiplatelet therapy (PG-PRT) from the perspective of US healthcare providers.

Methods

A decision-analytic model was used to simulate life-long medical costs and quality-adjusted life-years (QALYs) of three antiplatelet strategies in a hypothetical cohort of 60-year-old patients with acute coronary syndrome after a percutaneous coronary intervention: (a) universal clopidogrel (75 mg daily), (b) universal alternative antiplatelet therapy (prasugrel or ticagrelor), and (c) all PG-PRT patients were genotyped. Noncarriers of the CYP2C19 loss-of-function (LOF) allele received clopidogrel 75 mg daily. CYP2C19 LOF allele(s) carriers who were poor metabolizers received prasugrel or ticagrelor. CYP2C19 LOF allele(s) carriers who were intermediate metabolizers (IM) received high-dose clopidogrel (225 mg daily) and were tested for high on-treatment platelet reactivity (HTPR). IM patients with HTPR were switched to prasugrel or ticagrelor. Model inputs were derived from the literature.

Results

In base-case analysis, PG-PRT was the least costly (USD 71 887) strategy with highest QALYs gained (7.886 QALYs). Sensitivity analyses found universal clopidogrel to be the preferred strategy if the prevalence of the CYP2C19 LOF allele was less than 2.6% or the incidence of HTPR in IM patients was greater than 82.8%. In 10 000 Monte Carlo simulations, PG-PRT was less costly than universal clopidogrel by USD 91 [95% confidence interval (CI) 83–99; P=0.0499], with higher QALYs by 0.0257 (95% CI: 0.0256–0.0258; P<0.001). Compared with universal alternative antiplatelet therapy, PG-PRT was less costly by USD 2208 (95% CI: 2195–2221; P<0.001) and gained 0.0085 QALYs (95% CI: 0.0083–0.0087; P=0.0260).

Conclusion

PG-PRT seems to be cost-saving and effective for guiding selection of antiplatelet therapy in acute coronary syndrome patients undergoing percutaneous coronary intervention.

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