Combined therapy with proton pump inhibitors and clopidogrel - focus on cardiovascular risk

Aim. To analyze accessible studies on the problem of potential interaction of proton pump inhibitors and clopidogrel and to evaluate the influence of combined therapy with these pharmacologic agents on cardiovascular adverse effects development. Materials and methods. Data from 43 foreign and Russian literature sources including international clinical guidelines, randomized and prospective clinical studies, cohort and retrospective studies, clinical registries, metaanalyses and systematic reviews were analyzed. Results. The issue of proton pump inhibitors and P2Y12 thrombocytes receptors inhibitor clopidogrel interaction is discussed in the context of cardiovascular risk and influence on essential adverse cardiovascular events (including acute coronary syndrome, stent thrombosis, necessity of myocardial revascularization, stroke, myocardial infarction, all-cause and/or cardiovascular mortality, symptomatic or non- symptomatic gastrointestinal hemorrhage) in patients taking dual antiplatelet therapy. Standpoints of current international guidelines concerning possibility and necessity of theses medicines use in combination are presented. Data from a significant amount of studies on proton pump inhibitors influence on clopidogrel clinical effectiveness are discussed. The results of analyzed studies demonstrate increased risk of adverse cardiovascular events in the group of patients with ischemic heart disease who receive concomitant treatment with proton pump inhibitors. In particular, in several metaanalyses it was demonstrated that concurrent administration of acetosalicylic acid, clopidogrel, and proton pump inhibitors reduces frequency of gastrointestinal hemorrhage, but at the same time increases risk of major adverse cardiovascular events, increases probability of stent thrombosis and necessity of revascularization. Nevertheless, these results were not confirmed in multiple randomized clinical studies. Conclusion. Considering available literature data we can make a conclusion of necessity of large well-orchestrated randomized clinical studies conduction in order to find a conclusive answer on safety of proton pump inhibitors use in patients after percutaneous coronary intervention or coronary artery bypass surgery, including patients after acute coronary syndrome.

clopidogrel, proton memory inhibitors, major adverse cardiovascular events, cardiovascular risk, evidence-based medicine