"Clopidogrel with or without Omeprazole in Coronary Artery Disease". The New England Journal of Medicine. 2010.

Clinical Question

Does the addition of a proton-pump inhibitor (PPI) to dual antiplatelet therapy with aspirin and clopidogrel reduce gastrointestinal complications without increasing cardiovascular events?

Bottom Line

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.

Major Points

Guidelines

No guidelines were specified reflecting the results of this trial at the time of publication.

Design

- 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)

Population

- 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

Interventions

- CGT-2168 (fixed-dose combination of clopidogrel 75 mg and omeprazole 20 mg) vs. clopidogrel alone

Outcomes

- 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

Criticisms

- 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

Funding

Cogentus Pharmaceuticals; trial ended prematurely when the sponsor became defunct.

Further Reading

- ClinicalTrials.gov number, NCT00557921