Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy

Abstract

The ESC NSTEMI and STEMI guidelines1,2 and an ACCF/ACG/AHA consensus document3 recommend treatment with proton pump inhibitors (PPIs) in patients treated with dual antiplatelet treatment (DAPT) during the initial phase of an acute coronary syndrome (ACS) (ESC Class 1A recommendation), particularly in patients with a history of GI bleeding or peptic ulcer. Several studies have raised concerns that many PPIs, especially omeprazole, might diminish the antiplatelet effects of clopidogrel, most likely through inhibition of CYP2C19 and, consequently, the conversion of clopidogrel into its active metabolite.4,5 The aim of this position paper is to review the pharmacokinetic background of the interactions between these drugs, and their consequences on clinical outcomes, and to present suggestions for management of this important issue. Several agents widely used in patients on acetylsalicylic acid (ASA) may interact with the antiplatelet effects of ASA, but none through the CYP2C9 pathway by which ASA is metabolized. Recently, it has been reported that concomitant use of PPIs reduces the protective efficacy of ASA in patients with ischaemic heart disease.6,7 A case–control study investigated the antiplatelet effect of ASA in 418 ASA-treated CVD patients, 54 of whom were also treated with PPIs.7 Patients receiving PPIs had reduced antiplatelet effect of ASA, as shown by greater residual platelet aggregation responses. However, interaction between PPI and ASA is controversial.8 Potential clinical implications of these findings were explored by a registry study in a large population of ASA-treated patients with first time myocardial infarction.6 Even after adjusting for baseline variables with multivariate analysis and propensity score matching, PPI use was still significantly associated with ∼50% more ischaemic cardiovascular events. A sensitivity analysis showed no increase in risk related to the use of H2 receptor blockers.6 Suggested explanations for the …