PPIs attenuated antiplatelet effects somewhat, but outcomes were similar with or without PPIs.

Recent studies have suggested that proton-pump inhibitors (PPIs) can interfere with the antiplatelet effects and clinical effectiveness of clopidogrel after percutaneous coronary intervention (PCI), perhaps by inhibiting hepatic conversion of the clopidogrel prodrug to its active metabolites (JW Gen Med Mar 12 2009). To assess interactions among PPI use, platelet function, and cardiovascular outcomes, researchers examined data from two industry-sponsored randomized trials in which clopidogrel was compared with a newer thienopyridine, prasugrel, in patients with acute coronary syndromes who underwent planned PCIs.

In one trial, 201 patients were randomized to prasugrel or to high-dose clopidogrel; 53 patients (26%) were taking PPIs at randomization. Platelet function was measured frequently on the first day and once again after 2 weeks. In both groups, PPI use was associated with less inhibition of platelet aggregation at most measurement points; many of these differences approached or reached significance.

In the second trial, 13,608 patients were randomized to prasugrel or standard-dose clopidogrel and were followed for more than 1 year; 33% were taking PPIs at randomization. No association was found between PPI use and the primary clinical endpoint of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke for patients in either group.

Comment: PPIs modestly attenuated inhibition of platelet aggregation in patients who received clopidogrel or prasugrel, but this effect did not lead to an excess of important adverse cardiovascular events. The authors suggest that, when clinically indicated, PPIs can be used safely along with antiplatelet drugs in most patients.