Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.

BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.

Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.

BACKGROUND: Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel. METHODS AND RESULTS: Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs. CONCLUSIONS: Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.