Abstract 3999: Baseline Proton Pump Inhibitor Use is Associated with Increased Cardiovascular Events With and Without the Use of Clopidogrel in the CREDO Trial

Abstract

Ex vivo data suggest that a pharmacokinetic interaction may exist between proton pump inhibitors (PPIs) and clopidogrel, decreasing the antiplatelet effect of the latter. We assessed that baseline PPI use would increase the 28-day and 1-year composite endpoints in patients undergoing, or at high likelihood of undergoing, PCI randomized to a loading dose and 1-year clopidogrel versus just 4 weeks of clopidogrel, in addition to daily aspirin, in the CREDO trial. Twenty-eight day (Death/MI/UTVR) and 1-year (Death/MI/Stroke) primary endpoints were analyzed based on PPI use at study entry. For each primary endpoint, Cox proportional hazard or logistic regression models were fit to identify the risk of PPI use in the patients receiving clopidogrel, placebo, and in the overall population. Clopidogrel reduced adverse events at 1-year to an approximately similar degree whether or not patients were on a PPI (Table 1 ). PPI use also increased the incidence of the 28-day endpoint in patients receiving clopidogrel or placebo, although this did not achieve significance (Table 1 ). Additionally, PPI use was independently associated with the 28 day (HR 1.6, 95% CI 1.08 –2.5, p=0.022) and 1 year (HR 1.5, 95% CI 1.1–2.1, p=0.012) endpoints in the overall trial population. Baseline PPI was associated with an increase in cardiovascular events at 1-year in both patients receiving clopidogrel and the overall trial population. However, clopidogrel reduced adverse events at one year to an approximately similar degree whether or not patients were on a PPI. Table 1