More research has been published that investigates the relationship between use of proton pump inhibitors (PPIs) and clopidogrel with cardiovascular risk.
The Annals of Internal Medicine published the results of a Danish cohort study that aimed to assess the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults admitted to hospital for myocardial infarction.
Data for 56,406 patients were reviewed for a primary outcome of readmission for heart attack, stroke or cardiovascular death. In patients prescribed both a PPI and clopidogrel compared to those who only received clopidogrel that hazard ratio was 1.29 (95% CI 1.17-1.42). In patients who did not receive clopidogrel at all, the hazard ratio for those who were prescribed a PPI was 1.29 (95% CI, 1.21-1.37) compared to those who were not prescribed a PPI.
The authors conclude that, "proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction".
The New England Journal of Medicine has published the results of a randomised trial that aimed to assess the rate of gastrointestinal and cardiovascular complications in patients in patients receiving dual antiplatelet therapy (aspirin and clopidogrel) with randomly assigned omeprazole or placebo.
The study aimed to recruit 5,000 participants but was terminated early when funding was lost. However, data for 3,761 participants were available for analysis. The gastrointestinal (GI) outcome was a composite of overt or occult bleeding, symptomatic gastro-duodenal ulcers or erosions, obstruction or perforation. Patients who were assigned to treatment with omeprazole were at a lower risk of a GI event (hazard ratio 0.34, 95% CI 0.18-0.63; P<0.001). The cardiovascular outcome was a composite of death from cardiovascular causes, non-fatal myocardial infarction, revascularisation or stroke. There was no statistical difference in event rates in patients assigned to treatment with omeprazole (hazard ratio 0.99, 95% CI 0.68-1.44; P=0.96).
The authors of this study conclude that, "among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding. There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI".
Action: Clinicians should be aware of this evolving evidence. More research is needed to explore the effects of PPIs on cardiovascular outcomes. In the meantime it may be prudent to reduce doses or stop treatment with PPIs, if possible, in patients with existing cardiovascular disease.