Conflicting results between randomized trials and observational studies on the impact of proton pump inhibitors on cardiovascular events when coadministered with dual antiplatelet therapy: systematic review

Circ Cardiovasc Qual Outcomes. 2015 Jan;8(1):47-55. doi: 10.1161/CIRCOUTCOMES.114.001177. Epub 2015 Jan 13.

Abstract

Background: Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non-ST-segment-elevation myocardial infarction patients.

Methods and results: We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole.

Conclusions: Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non-ST-segment-elevation myocardial infarction treated with DAPT are warranted.

Keywords: acute coronary syndrome; proton pump inhibitors.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Angina, Unstable / diagnosis
  • Angina, Unstable / drug therapy*
  • Angina, Unstable / mortality
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / mortality
  • Drug Interactions
  • Drug Therapy, Combination
  • Evidence-Based Medicine
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / mortality
  • Gastrointestinal Hemorrhage / prevention & control*
  • Humans
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Observational Studies as Topic*
  • Odds Ratio
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic*
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors