Using clopidogrel, PPIs increases cardiac damage risk: Study

Medical University of ViennaAug 31 2010

Patients with coronary artery disease undergoing stent implantation are often prescribed the antiplatelet drug, clopidogrel. This drug prevents blood clots, but is known to have a side-effect that can cause stomach bleeding. Consequently, many users are also prescribed a proton pump inhibitor (PPI). Now, however, a meta-analysis of almost 160,000 patients carried out at the Medical University of Vienna and Wilhelminenhospital, Vienna, has shown that simultaneous use of these drugs can increase the risk of cardiac damage.

Previous studies of this subject have given conflicting results, and the only clinical trial initiated to gather evidence was not completed. A research team led by Doctor Jolanta Siller-Matula of the Medical University of Vienna and Professor Kurt Huber of Wilhelminenhospital, Vienna therefore undertook a detailed analysis into the simultaneous use of clopidogrel and PPIs. Of the large study population taking clopidogrel, 34 percent were also taking PPIs.
 
Professor Kurt Huber noted, "The team found that PPI use increased the risk of major cardiovascular events by 29 percent and increased the risk of myocardial infarction by 31 percent. On the plus side, however, the evidence also showed that using clopidogrel alongside a PPI had no effect on mortality  while the risk of developing gastrointestinal bleeding decreased by 50 percent".

It is important to note that attenuation of the clopidogrel effect will vary according to the type of PPI being used. For example, negative effects were demonstrated with omeprazole, while pantoprazole appeared to be quite safe. Consequently, there is an opportunity for the scientific community to undertake further work on this topic, and perform randomised trials to investigate which PPIs should be avoided by clopidogrel users.

Commenting on the study, Doctor Siller-Matula said: "Given that thousands of patients undergo coronary stenting each year, and that clopidogrel is widely used to prevent blood clots that could lead to heart attacks, our findings could have significant implications for many patients. The results show that using clopidogrel and PPIs simultaneously may restrict blood flow to the heart. Therefore, our advice to clinicians is to only prescribe gastric protection when absolutely necessary, and then to prescribe PPIs without negative effects, such as pantoprazole. We do not recommend that patients stop taking clopidogrel."