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Clopidogrel and proton pump inhibitors: in theory and practice

▸ O’Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009;374:989–97.

Previous observational studies have provided conflicting clinical data about the effects of various proton pump inhibitors (PPIs) on outcomes in patients given the thienopyridine antiplatelet agent clopidogrel, leading to warnings and uncertainty about concomitant use of these widely used drugs. However, these observational studies are heavily confounded by the fact that patients taking concomitant PPIs are generally older and have more co-morbidities than do those not on a PPI. Fortunately, the TIMI investigators have brought some rationality to this arena by conducting some analyses in their large-scale clinical trials. First, PPI treatment attenuated the pharmacodynamic effects of clopidogrel, and to a lesser extent those of the newer thienopyridine prasugrel, in patients undergoing elective percutaneous coronary intervention. Secondly, PPI treatment did not affect the primary vascular outcomes of patients given clopidogrel or prasugrel in 13 608 patients with acute coronary syndromes in the TRITON-TIMI trial (33% of whom were on a PPI at randomisation) (fig 1). These findings provide reliable evidence that there is no need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel or prasugrel. However, further trial evidence of gastroprotective treatment strategies to reduce bleeding hazards with antiplatelet agents, which underpin many of these arguments, are also required. …

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