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Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial
Muthiah Vaduganathan1, Christopher P Cannon2, Byron L Cryer3
1Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Mass.
Insights
Proton-pump inhibitors (PPIs) reduce gastrointestinal events in patients on dual antiplatelet therapy (DAPT) after acute coronary syndrome or PCI. Omeprazole showed efficacy without increasing cardiovascular events in high-risk patients.
Area of Science:
- Cardiology
- Gastroenterology
- Pharmacology
Background:
- Proton-pump inhibitors (PPIs) are known to reduce gastrointestinal (GI) events in patients on dual antiplatelet therapy (DAPT).
- Limited data exist on PPI efficacy and safety in high-risk cardiovascular subsets post-acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI).
Purpose of the Study:
- To evaluate the efficacy and safety of omeprazole versus placebo in high-risk cardiovascular patients undergoing DAPT.
- To assess omeprazole's impact on GI and cardiovascular events in specific patient subsets (PCI and ACS).
Main Methods:
- Post hoc analysis of the COGENT trial involving patients on DAPT (aspirin and clopidogrel).
- Subsets analyzed: patients undergoing PCI within 14 days (n=2676) and patients with ACS (n=1573).
- Unadjusted Cox proportional hazards models were used to estimate effect sizes.
Main Results:
- In PCI patients, omeprazole significantly reduced GI events (1.2% vs 2.7%; HR 0.43) without increasing cardiovascular events (5.4% vs 6.3%).
- In ACS patients, omeprazole lowered GI events (1.1% vs 2.7%; HR 0.37) without a significant excess in cardiovascular events (5.6% vs 4.5%).
Conclusions:
- PPI therapy, specifically omeprazole, effectively reduces GI bleeding risk in high-risk cardiovascular patients on DAPT.
- Omeprazole did not significantly increase major cardiovascular events in these high-risk subsets, supporting its use for gastroprotection.
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.
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