Level 1: Mid-level evidence
Two recent retrospective studies have examined cardiovascular outcomes associated with combining clopidogrel with proton-pump inhibitors (PPIs). A case-control study with 13,636 elderly patients taking clopidogrel after hospitalization for acute MI analyzed PPI use in patients re-admitted for acute MI within 90 days compared with event-free controls (CMAJ. 2009;180:713-718; available at www.cmaj.ca/cgi/content/full/180/7 /713, accessed July 14, 2009). Because pantoprazole is a much weaker inhibitor of cytochrome P450 2C19 than other PPIs, exposure to this agent was studied separately. Use of PPIs (other than pantoprazole) within 30 days of discharge was significantly higher among the patients with MI than controls (20.2% vs. 14.5%), but there was no difference in the rate of pantoprazole usage (6.1% vs. 6.3%). There were no differences in mortality at 90 days or at one year. No relation was found between rehospitalization and use of H2 blockers.

In a cohort study of 8,205 patients with acute coronary syndrome (ACS) taking clopidogrel at hospital discharge, concomitant use of PPIs was associated with a higher rehospitalization rate for ACS (14.6% vs. 6.9%, P <.05, NNH 12) and more revascularization procedures (15.5% vs. 11.9%, P <.05, NNH 27) compared with nonuse (JAMA. 2009; 301:937-944). These differences remained significant after adjustment for baseline differences in age and comorbidities. There was also a nonsignificant increase in all-cause mortality in the PPI group (19.9% vs. 16.6%). Use of PPIs was not associated with either death or rehospitalization for ACS in an additional cohort of 6,450 patients who were not taking clopidogrel after hospital discharge.