October 6th, 2010
Study Finds No Evidence for Clopidogrel-Omeprazole Interaction
A large clinical trial has found no evidence that omeprazole interferes with the cardiovascular efficacy of clopidogrel. COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) randomized 3873 patients eligible for dual antiplatelet therapy to receive aspirin, clopidogrel, and either omeprazole or placebo. The COGENT investigators had planned to enroll 5000 patients, but the trial was terminated early when the sponsor ran out of money.
Gastrointestinal events occurred in 2.9% of the placebo group compared with 1.1% of the omeprazole group (p<0.001). There was no significant difference in the rate of cardiovascular events between the two groups (5.7% in the placebo group versus 4.9% in the omeprazole group; p=0.096). In their report in the New England Journal of Medicine, the authors write that the study “provides reassurance that there is no clinically significant cardiovascular interaction between PPIs and clopidogrel.”
Sanjay Kaul provided the following points on the clinical implications of COGENT:
- No clinically relevant adverse CV interaction between clopidogrel and omeprazole in COGENT, a prospective randomized trial. The cardiovascular results refute the previous findings based on observational studies; however, they confirm the post hoc assessments of other randomized trials such as CREDO and TRITON. The current findings do not support the need to avoid concomitant use of omeprazole in patients treated with clopidogrel. However, given the limited number of cardiovascular events in the COGENT trial and the fact that the study was conducted predominantly in Caucasians where the frequency of loss-of-function CYP2C19 genetic polymorphism is low (2-3%), one cannot completely rule out the possibility of an adverse interaction between clopidogrel and omeprazole (or other PPIs) in other populations where the frequency of CYP2C19 genetic polymorphism is high (for example, Asians).
- Substituting an H2 receptor antagonist such as ranitidine for a PPI, especially in those for whom there is no compelling indication for a PPI, should remain an important consideration during concomitant therapy with clopidogrel.
- Interpret information from observational studies with caution, as they are often subject to confounding and bias and can yield potentially misleading results.
- The findings raise questions about the relationship between ex vivo platelet function assays and clinical outcomes. Platelet function assay-guided treatment decisions are not ready for prime time.
- Finally, should regulatory agencies and professional societies change label or practice recommendations based on limited data?