Abstract 12092: Proton Pump Inhibitor Use is Likely a Marker for, Rather than a Cause of, a Higher Risk of Cardiovascular Events: Insights from PLATO
Background: Conflicting data exist regarding the potential adverse interaction between clopidogrel and proton pump inhibitors (PPIs). PPIs inhibit the cytochrome P450 2C19 isoenzyme and conversion of clopidogrel into its active metabolite. In contrast, ticagrelor is an ADP P2Y12 inhibitor that does not require biotransformation and has no known interaction with PPIs.
Objectives and Methods: The association between PPI use and clinical outcomes for acute coronary syndrome patients (pts) randomized to clopidogrel or ticagrelor in the PLATO trial was examined using a multivariable Cox model with propensity adjustment and landmark analysis. The primary endpoint was the 1-year composite of CV death, MI or stroke. PPI use was at the physician's discretion. Findings 18601 of 18624 pts had documentation regarding PPI use prior to randomization; 6539 (35.2%) pts were taking a PPI. PPI-treated pts had significantly higher risk scores, were more likely to be older, have a NSTEMI, history of CV, renal, and peptic ulcer disease, and a lower baseline hemoglobin concentration. Regardless of randomized P2Y12 inhibitor treatment, pts on a PPI tended to have higher primary endpoint and bleeding rates (Table). Pts on non-PPI gastric acid suppressive drugs (e.g. H2 receptor antagonists) prior to randomization were at similar risk to those on a PPI while pts on no gastric therapy were at significantly lower risk of the primary endpoint. Landmark analyses accounting for PPI use post-randomization showed no increased risk of the primary endpoint in those receiving a PPI. The benefit of ticagrelor over clopidogrel on the primary endpoint was consistent and remained significant, irrespective of the use of a PPI.
Conclusions: The apparent association between PPI and clopidogrel use and adverse events is highly confounded. PPI use may simply be a marker for, rather than a cause of, a higher risk of CV events. Regardless of PPI use, ticagrelor was superior to clopidogrel in preventing ischemic events.
- © 2010 by American Heart Association, Inc.