"Clopidogrel with or without Omeprazole in Coronary Artery Disease". The New England Journal of Medicine. 2010.
Links to original sources: Wiki Journal Post Full Journal Article
Does the addition of a proton-pump inhibitor (PPI) to dual antiplatelet therapy with aspirin and clopidogrel reduce gastrointestinal complications without increasing cardiovascular events?
Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding without significantly increasing cardiovascular events. However, the study's premature termination limits the conclusiveness regarding cardiovascular safety.
Previous studies indicated that PPIs could reduce gastrointestinal complications from long-term antiplatelet therapy, and concerns existed about potential interactions between PPIs and clopidogrel reducing clopidogrel's efficacy. The COGENT trial was designed to evaluate the efficacy and safety of concomitant administration of clopidogrel and PPIs in patients with coronary artery disease on dual antiplatelet therapy.
No guidelines were specified reflecting the results of this trial at the time of publication.
- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial - N=3,873 patients with indications for dual antiplatelet therapy - Randomized to clopidogrel with either omeprazole or placebo, in addition to aspirin - Trial prematurely terminated due to sponsor's financial issues - Median follow-up: 106 days (max 341 days)
- Inclusion criteria: Patients ≥21 years, indication for dual antiplatelet therapy for at least 12 months - Exclusion criteria: Need for PPIs, H2-receptor antagonists, or certain anti-inflammatory drugs; recent fibrinolytic therapy - Baseline characteristics: Well-matched between treatment groups
- CGT-2168 (fixed-dose combination of clopidogrel 75 mg and omeprazole 20 mg) vs. clopidogrel alone
- Primary gastrointestinal end point: Composite of overt/occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation - Primary cardiovascular end point: Composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke - Notable secondary end point: Symptoms of gastroesophageal reflux disease
- Premature termination meant smaller number of events, limiting power - Wide confidence intervals for the cardiovascular end point, so no significant interaction could be considered conclusive - The use of a single-pill formulation with different release kinetics from generic omeprazole
Cogentus Pharmaceuticals; trial ended prematurely when the sponsor became defunct.
- ClinicalTrials.gov number, NCT00557921