proton pump inhibitors
Clopidogrel and Proton Pump Inhibitors: The need for reliable evidence
Previous observational studies and small randomised trials have given conflicting clinical data about the effects of various proton pump inhibitors (PPIs) on outcomes in patients given clopidogrel, leading to warnings and uncertainty about taking these drugs at the same time.
However, when you look at these studies they are heavily confounded, or to put it simpler the results are distorted by the fact that patients taking the two drugs together are generally older and have more co-morbidities than do those not on a PPI.
Fortunately, the TIMI investigators have recently brought some rationality to this arena by conducting analyses in their large-scale clinical trials. Firstly, PPI treatment did have a pharmacological interaction with clopidogrel, in patients undergoing coronary intervention. Secondly, PPI treatment did not affect the primary cardiovascular outcomes of patients given clopidogrel in a trial of more than 13,000 patients with acute coronary syndromes. For the first time these findings provide reliable evidence that there is no need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel.
This study highlights another important area in which more joined-up thinking is required. In response to mentioned smaller observational studies with significant confounding, both the European Medicines Agency and the US Food and Drug Administration released statements or communications warning of a potential interaction between PPIs and clopidogrel, and discouraging their combined use in the absence of a 'strong' indication. Instead of causing widespread uncertainty and panic to thousands of clinicians and patients, would it not have been more sensible for them to work with academia and the pharmaceutical industry to resolve these questions more reliably? The EMEA and FDA hold great power as regulatory authorities, but with this comes great responsibility - if we cannot trust the evidence from them, who can we trust?
Neeraj Bhala is a MRC Research Fellow at the Clinical Trial Service Unit University of Oxford, UK and regularly meets in the 'Golden Triangle' with the founders of TrustTheEvidence