Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial.
BACKGROUND
Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention.


METHODS
All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up.


RESULTS
Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P = .02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P = .05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P = .27).


CONCLUSIONS
PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.
['Vaduganathan|Muthiah|M|', 'Cannon|Christopher P|CP|', 'Cryer|Byron L|BL|', 'Liu|Yuyin|Y|', 'Hsieh|Wen-Hua|WH|', 'Doros|Gheorghe|G|', 'Cohen|Marc|M|', 'Lanas|Angel|A|', 'Schnitzer|Thomas J|TJ|', 'Shook|Thomas L|TL|', 'Lapuerta|Pablo|P|', 'Goldsmith|Mark A|MA|', 'Laine|Loren|L|', 'Bhatt|Deepak L|DL|', '|||']
D054058:Acute Coronary Syndrome D001241:Aspirin D000077144:Clopidogrel D004311:Double-Blind Method D004359:Drug Therapy, Combination D006471:Gastrointestinal Hemorrhage D006801:Humans D009853:Omeprazole D062645:Percutaneous Coronary Intervention D010975:Platelet Aggregation Inhibitors D054328:Proton Pump Inhibitors D013988:Ticlopidine D016896:Treatment Outcome
Proton-pump inhibitors Acute coronary syndrome Percutaneous coronary intervention Bleeding Clinical outcomes Clinical trials Coronary artery disease