Proton pump inhibitors for prevention of bleeding episodes in cardiac patients with dual antiplatelet therapy – between Scylla and Charybdis?

Guidelines from national and international cardiac societies recommend dual antiplatelet therapy with aspirin and thienopyridines (clopidogrel, ticlopidine) in patients with acute coronary syndrome and patients undergoing percutaneous coronary intervention. The most-feared complication of antiplatelet therapy is hemorrhage. Long-term treatment with aspirin increased bleeding rates compared to placebo and similar bleeding rates were observed on clopidogrel. Dual antiplatelet therapy increased hemorrhage with the dose of aspirin administered impacting on increased bleeding rates. Concomitant treatment with a proton pump inhibitor (PPI) decreased bleeding rates in patients on antiplatelet therapy. An analysis of medical and pharmacy databases indicated a more than 3-fold increase in the incidence of myocardial infarction within 12 months after starting treatment with clopidogrel in patients on concomitant treatment with a PPI. This might be attributed to a drug-drug interaction between PPIs and clopidogrel because recent clinical studies showed that treatment with the PPI omeprazole attenuated the antiplatelet effect of clopidogrel most likely by inhibiting the formation of the active metabolite which carries the antiplatelet activity of the drug. Therefore, sufficiently powered prospective clinical studies in cardiac patients on dual antiplatelet therapy investigating the potential drug interaction between PPIs and the antiplatelet effect of clopidogrel are awaited eagerly.