AIM: Clopidogrel plus PPI use is safe, large Danish study finds

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Concomitant use of clopidogrel and a proton-pump inhibitor (PPI) does not appear to increase cardiovascular risk beyond that seen with PPIs alone, according to a study in the Sept. 21 issue of the Annals of Internal Medicine.

Previous research had suggested a drug interaction, with the FDA warning against using clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) with the PPI omeprazol (Prilosec, AstraZenica).

For this study, Mette Gitz Charlot, MD, from the University of Copenhagen in Hellerup, Denmark, and colleagues examined registry data on some 56,000 patients from all hospitals in Denmark discharged after first MIs. They found that 16 percent experienced the primary outcome (cardiovascular death or rehospitalization for MI or stroke) in the first year.

In adjusted analyses, risk for the primary outcome was similarly increased (by about one-third) among patients who received both a PPI and clopidogrel after MI and among those who received just a PPI, compared with those not receiving PPIs.

The hazard ratio for cardiovascular death or rehospitalization for MI or stroke for concomitant use of a PPI and clopidogrel among the cohort at 30 days after discharge was 1.29. The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29. No statistically significant interaction occurred between a PPI and clopidogrel, the authors wrote.

The authors said their findings "seem to refute concerns about increased risk for ischemic events during concomitant PPI and clopidogrel therapy."

"We found no evidence of drug interaction between clopidogrel and proton pump inhibitors," Charlot wrote in an email. "We did find an increased risk related to use of proton pump inhibitors but this risk was present whether patients were treated with clopidogrel or not. We believe that the observed increased risk represents residual confounding and it indicates just how different patients on and not on proton pump inhibitors are from one another."

In an accompanying editorial, Joao Paulo de Aquino Lima, MD, and James M. Brophy, MD, from Federal University of CearĂ¡ School of Medicine in Brazil and McGill University, Montreal, Quebec, respectively, asked how clinicians should interpret this information, especially with conflicting data from other studies.

"We propose that a critical systematic review of all of the evidence would certainly help, but that a meta-analysis that combines studies of very uneven scientific quality would not," they wrote.

They also suggested it would be helpful to review the current "understanding of the benefits of clopidogrel, as determined from randomized clinical trials; consider the magnitude of both the thrombotic and bleeding risks associated with clopidogrel and their possible attenuation with PPIs; and review the quality metrics of observational studies."