Clopidogrel plus PPI after hospitalization for ACS leads to increased risk of adverse outcomes

A retrospective cohort study published in the Journal of the American Medical Association demonstrated that concomitant use of clopidogrel and a proton-pump inhibitor (PPI) after hospital discharge for acute coronary syndrome (ACS) is associated with an increased risk of all-cause mortality and rehospitalization for ACS.

Data were collected as part of the Cardiac Care Follow-up Clinical Study, which compiled national data from the Veterans Health Administration (VHA) external peer-review program for quality monitoring. Patients with acute myocardial infarction (MI) or unstable angina who were discharged from 1 of 127 VHA medical centers between October 1, 2003, and January 31, 2006, and who were prescribed clopidogrel at hospital discharge were included in this study. Information on clopidogrel and PPI use was based on VA pharmacy refill data. The primary outcome was the combined end point of all-cause mortality or rehospitalization for acute coronary syndrome (MI or unstable angina) after index hospital discharge for ACS. Secondary outcomes included rehospitalization for ACS; revascularization procedures, percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery; and all-cause mortality.

A total of 8,205 patients with ACS were taking clopidogrel after hospital discharge. Of these patients, 63.9% were prescribed a PPI at discharge, during follow-up, or both, and 36.1% were not prescribed a PPI. The median follow-up was 521 days.

The primary end point occurred in 20.8% of patients taking clopidogrel without a PPI and in 29.8% of patients taking clopidogrel with a PPI; multivariable analysis demonstrated that the use of a PPI during clopidogrel treatment was associated with an increased risk of death or rehospitalization for ACS (adjusted OR=1.25; 95% CI, 1.11–1.41).

Patients taking a PPI with clopidogrel also demonstrated increased rates of recurrent hospitalization for ACS (14.6% vs 6.9%; PPP
The investigators also assessed whether the PPI itself was associated with adverse outcomes. Patients who did not take clopidogrel after hospital discharge but took a PPI did not demonstrate an increased risk of death or rehospitalization for ACS (adjusted OR=0.98; 95% CI, 0.85–1.13).

The authors suggested that, based on these results, “concomitant use of clopidogrel and PPI may be associated with an attenuation of the benefits of clopidogrel after hospitalization for ACS.” They discussed several limitations of their study, including over-the-counter (OTC) availability of omeprazole, a primarily male population, and lack of cause-specific mortality data. They concluded, “Pending further studies to confirm these results and prospectively assess cardiovascular outcomes for patients taking clopidogrel plus PPI vs clopidogrel without PPI, the results of this study may suggest that PPIs should be used for patients with a clear indication for the medication, rather than routine prophylactic prescription.”

Source
Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301:937–944.