PPI use reduces benefit of clopidogrel post-MI

Clinical Question

Does concomitant treatment with a proton pump inhibitor and clopidogrel after a myocardial infarction increase the risk of recurrent myocardial infarction?

Bottom Line

The use of a proton pump inhibitor (PPI) other than pantoprazole (Protonix) is associated with a significantly increased risk of recurrent myocardial infarction (MI) in patients already taking clopidogrel (Plavix). Consider prescribing pantoprazole if a PPI is needed in a post-MI patient. (LOE = 3b)


Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009;180(7):713-718.  [PMID:19176635]

Study Design





Outpatient (any)


Most PPIs inhibit cytochrome P450, an enzyme that helps convert clopidogrel from a prodrug to its active metabolite. Given the frequency with which post-MI patients take PPIs, often to counteract the effect of aspirin, it is important to know whether this results in a clinically important drug interaction. In this study, the authors used pharmacy, insurance, hospital, and death registry databases to identify a cohort of 13,636 patients given clopidogrel within 3 days of hospital discharge for an acute MI. They then identified 782 patients readmitted within 90 days for recurrent MI, determined if and when they took a PPI, and matched each of these patients with 3 patients who were current, previous, or remote users of a PPI. Current users were using a PPI within 30 days of the recurrent MI, previous users took a PPI between 31 and 90 days before the recurrent MI, and remote users used a PPI more than 90 days before the event. Theauthors then performed a multivariate analysis to adjust for age, sex, income, severity of illness, and 9 comorbid conditions associated with recurrent MI, as well as the use of other drugs that affect clopidogrel metabolism. After adjustment, they found that current users (but not previous or remote users) had a significantly increased risk of recurrent MI if they were taking a PPI (odds ratio [OR] = 1.27; 95% CI, 1.03 - 1.57). They looked at pantoprazole (Protonix) separately, since it does not inhibit cytochrome P450, and found no effect in patients taking this drug (OR = 1.02; 0.7 to 1.47). When you looked only at patients taking a non-pantoprazole PPI, the risk of recurrent MI was even greater (OR = 1.40; 1.1 - 1.77). The authors estimate that concomitant use of a non-pantoprazole PPI with clopidogrel is responsible for 7% to 14% of recurrent MIs, assuming that 20% to 40% of patients were taking one of these agents.