Increased CV risk with PPIs independent of concomitant clopidogrel
MedWire News: Myocardial infarction (MI) patients taking proton-pump inhibitors (PPIs) in isolation may have an increased risk for adverse cardiovascular (CV) events similar to those taking PPIs with concomitant clopidogrel, a Danish study suggests.
Mette Charlot (Copenhagen University Hospital, Hellerup, Denmark) and team explain that, contrary to previous reports, their findings illustrate that the increased CV risk associated with PPIs may in fact be "independent of concomitant use of clopidogrel."
They comment: "These results seem to refute concerns about increased risk for ischemic events during concomitant PPI and clopidogrel therapy."
To investigate, the researchers observed the outcomes of 56,406 MI patients taking a PPI and clopidogrel (n=6753), a PPI alone (n=8889), clopidogrel alone (n=17,949), or neither drug (n=22,815) over a 1-year follow-up period.
By the end of the follow-up period, 9137 patients had experienced the primary outcome of combined CV death, MI rehospitalization, or stroke.
Writing in the Annals of Internal Medicine, the team reports that compared with patients not taking a PPI, those taking concomitant clopidogrel and PPI, and those taking only PPI both had a 1.29-fold increase in risk for the primary outcome at 30 days. (p<0.001 for both).
The effect of the interaction between PPI and clopidogrel was a nonsignificant 0.98, thus indicating no significant additive effect of both drugs on the risk for adverse CV events.
Of the 15,642 patients taking PPIs, 30.0% took pantoprazole, 17.9% took lansoprazole, 17.4% took omeprazole, 34.0% took esomeprazole, and 0.01% took rabeprazole. On subanalysis, there was no difference in the level of risk for the primary outcome among the various types of PPIs.
The researchers comment, however, that baseline confounders may have contributed to their finding of an increased CV risk with PPI use independent of clopidogrel, and this requires further study.
In an accompanying editorial, Joao de Aquino Lima (Federal University of Ceará School of Medicine, Fortaleza, Brazil) and James Brophy (McGill University, Montreal, Quebec, Canada) commented: "Elderly patients with ACS who receive combination antiplatelet regimes have a four- to five-fold increase in their risk for serious gastrointestinal bleeding, which can be reduced with PPIs."
They therefore advised of a need for regulatory bodies to fully consider all relevant health outcomes when appraising the risks and benefits of PPIs before issuing further recommendations on PPI use.
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By Lauretta Ihonor