The Society For Cardiovascular Angiography And Interventions

The Society for Cardiovascular Angiography and Interventions 2400 N Street, NW, Suite 500, Washington, DC USA 20037-1153 (800) 992-7224 Fax (202) 689-7224 e-mail: [email protected] www.scai.org

ID: O-11 Session Location: Tiberius 2 and 3 Session Time: Wednesday, May 6, 10:30 - 10:45 am (Pacific Time) Press Conference Time: Wednesday, May 6, 11:30 am (Pacific Time) Category: Oral Abstracts, Late-Breaking Clinical Trial A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study Eric J. Stanek, PharmD1, Ronald E. Aubert, PhD1, David A. Flockhart, MD,PhD2, Rolf P. Kreutz, MD2, Jianying Yao, MS1, Jeffrey A. Breall, MD,PhD2, Zeruesenay Desta, PhD2, Todd C. Skaar, PhD2, Felix W. Frueh, PhD1, J. Russell Teagarden, MS1, Robert S. Epstein, MD1 1 Medco Health Solutions, Inc., Franklin Lakes, NJ 2 Indiana University School of Medicine, Indianapolis, IN Background Previous studies have demonstrated an increased risk of cardiovascular events in patients taking clopidogrel among carriers of a reduced-function cytochrome P450 2C19 allele or among those on concomitant proton pump inhibitor (PPI) therapy, both presumably related to diminished metabolic activation of clopidogrel. However, detailed analysis of the effect of individual PPI agents in a large population is lacking. Methods The effect of individual PPIs on the risk of hospitalization for major adverse cardiovascular events (MACE; composite of myocardial infarction, unstable angina, transient ischemic attack/stroke, coronary revascularization, or cardiovascular death) over 1 year was investigated in the Clopidogrel Medco Outcomes Study database of 16,690 patients adherent to clopidogrel following coronary stenting. In this study, the risk of MACE was significantly higher in patients on any PPI (N=6828; 25.1%) vs. no PPI (N=9862; 17.9%) [adjusted hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.39-1.64)]. Individual PPIs with sufficient sample size (N≥674) to detect a 25% increase in 1-year incidence of MACE vs. no PPI with 80% power (α=0.05) included for this analysis were omeprazole (N=2307), esomeprazole (N=3257), pantoprazole (N=1653), and lansoprazole (N=785), representing 96% of all PPI use. One-year MACE incidence and age/sex/comorbidity adjusted risk [Cox proportional hazards; HR (95%CI)] for each agent were compared to no PPI therapy. Results Patients on PPIs were older (mean age 67-69 years vs. 65 years), more frequently female (37%-40% vs. 26%), and had a higher prevalence of comorbidities than patients not on a PPI. Median duration of PPI exposure ranged from 287 days (pantoprazole) to 305 days (omeprazole, esomeprazole). Mean daily dose was ≤20mg in 81% on omeprazole, 21-40mg in 89% on esomeprazole, ≤40mg in 92% on pantoprazole, and 16-30mg in 83% on lansoprazole. Each PPI agent was associated with an increased incidence and risk of MACE vs. no PPI (17.9%): omeprazole [25.1%; HR 1.39 (1.22-1.57), p<0.0001], esomeprazole [24.9%; HR 1.57 (1.40-1.76), p<0.0001], pantoprazole [29.2%; HR 1.61 (1.411.88), p<0.0001], lansoprazole [24.3%; HR 1.39 (1.16-1.67), p=0.0004]. An exploratory analysis of rabeprazole was inconclusive due to limited power and sample size (N=298). The incidence of hospitalization for upper gastrointestinal bleeding was 0.07% in patients not on a

PPI and 1.1% for any PPI (omeprazole 0.82%, esomeprazole 1.11%, pantoprazole 2.54%, lansoprazole 0.76%). Conclusions Concomitant use of clopidogrel with omeprazole, esomeprazole, pantoprazole, or lansoprazole after coronary stenting was associated with an increased risk of MACE compared to clopidogrel without a PPI. More data are needed to establish if newer PPIs (rabeprazole, dexlansoprazole) also attenuate the benefit of clopidogrel.