PPIs don’t dampen the efficacy of clopidogrel, according to the results of COGENT, an important new randomized study presented at TCT by Deepak Bhatt. The study may finally put to rest the considerable concern this issue has raised in the past few years.
The trial randomized 3,627 patients with ACS receiving clopidogrel to receive either omeprazole or placebo. (The investigators had hoped to enroll 5,000 patients but the trial was terminated early when the sponsor, Cogentus, went into bankruptcy.)
There was absolutely no difference in the incidence of cardiovascular events between the two arms. However, as might be expected, there were fewer GI events in the omeprazole group than in the placebo group (38 vs 67 events, p=0.007).
Bhatt noted that “the results call into question the exact relationship between ex vivo platelet assays and clinical outcomes, especially with respect to assessing drug interactions.”
A story on MedPage Today quoted Chris Cannon saying that he gives PPIs to patients receiving antiplatelets “based on the advice of the gastroenterologists.”
Here are a few links to previous CardioBrief stories on this topic:
- ESC: TIMI study offers reassurance on concomitant use of PPIs and antiplatelets (August 31, 2009)
- Medco study: PPIs reduce clopidogrel efficacy post-stenting (May 6, 2009)
Here is the press release from the CRF:
Cogent trial shows lack of adverse interaction between clopidogrel and stomach medicine
SAN FRANCISCO, CA – SEPTEMER 24, 2009 – Results from a late breaking clinical trial called COGENT demonstrate that the combination of giving patients clopidogrel, a blood thinner commonly prescribed to patients with cardiovascular disease, and stomach medicines such as omeprazole, known as proton pump inhibitors (PPIs), did not lead to adverse events, as some prior studies had suggested. The results were presented at the 21st annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium, sponsored by the Cardiovascular Research Foundation (CRF).
COGENT is the first randomized assessment of administering clopidogrel and PPIs, which reduce the production of gastric acid, on clinical events. The trial involved 3,627 patients at 393 sites. Follow up was limited due to early termination of the trial.
Internal bleeding is a common adverse effect of antiplatelet or blood thinner therapies, such as clopidogrel. The gastrointestinal tract is the most common location for this type of bleeding, which often occurs in the form of peptic ulcer disease. The purpose of the trial was to determine whether the administration of clopidogrel and omeprazole is safe and effective in reducing the incidence of gastrointestinal bleeding and symptomatic ulcer disease in the setting of concomitant aspirin therapy.
The primary endpoint of the trial was a composite of upper gastrointestinal clinical events, including gastroduodenal bleeding, symptomatic gastroduodenal ulcer, and persistent pain with multiple gastric erosions, obstruction or perforation.
There was a significant reduction in gastrointestinal events with PPI use. This had not been previously demonstrated in patients receiving aspirin and clopidogrel.
“Further research is needed to define the optimal strategy to reduce GI events in patients on antithrombotic therapy, though prophylactic PPI use seems promising,” said lead investigator, Deepak L. Bhatt, MD, MPH, Chief of Cardiology at VA Boston Healthcare System and Director, Integrated Interventional Cardiovascular Program at Brigham and Women’s Hospital and the VA Boston Healthcare System.
About CRF and TCT
The Cardiovascular Research Foundation (CRF) is an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with cardiovascular disease through research and education. Since its inception in 1991, CRF has played a major role in realizing dramatic improvements in the lives of countless numbers of patients by establishing the safe use of new technologies and therapies in the subspecialty of interventional cardiology and endovascular medicine.
Transcatheter Cardiovascular Therapeutics (TCT) is the annual scientific symposium of the Cardiovascular Research Foundation. TCT gathers leading medical researchers and clinicians from around the world to present and discuss the latest developments in the field of interventional cardiology and vascular medicine.
For more information, please visit http://www.crf.org.