Clopidogrel and PPI, warfarin management, and rural pharmacists' competence

Abstract

Clopidogrel and PPI Stockl et al.1 concluded that “patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone.” Patients taking clopidogrel and a proton pump inhibitor (PPI) (n = 1,033) were compared with a matched group of patients taking clopidogrel alone. Propensity score matching corrected potential selection bias by balancing covariates between the two groups of patients. Patients included in the clopidogrel plus PPI group were dispensed a PPI with one or more days’ supply overlapping the index date and at least one refill within 90 days. The clopidogrel-alone group patients were not dispensed a PPI 90 days before or after the index date. Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for myocardial infarction (MI) (adjusted hazard ratio 1.93 [95% CI 1.05–3.54]; P = 0.03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64 [1.16– 2.32]; P = 0.005) than patients receiving clopidogrel alone. Implications. Patients taking clopidogrel and a PPI were at higher risk of rehospitalization. Reduced action of clopidogrel may result from competitive metabolic effects of the PPIs on cytochrome P450 (CYP)2C19. Also, CYP2C19 variant allele carriers have lower capacity to metabolize clopidogrel into its active metabolite and inhibit platelet activation.2 Does the higher risk of rehospitalization associated with taking a PPI potentially have a genetic component? Further study is needed of therapy based on genetic testing among patients at high risk of acute gastrointestinal bleeding where a PPI is indicated.