title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.). chiara.melloni@duke.edu.
authors.forename: Chiara
authors.initials: C
authors.lastname: Melloni
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Washam
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: Sharif A
authors.initials: SA
authors.lastname: Halim
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: Victor
authors.initials: V
authors.lastname: Hasselblad
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Mayer
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Heidenfelder
authors.affiliation: From the Duke Clinical Research Institute, Duke University Medical Center (C.M., W.S.J., S.A.H., V.H., B.L.H., R.J.D.); Duke Heart Center (J.B.W.), Duke University Medical Center, Durham, NC; and Division of Endocrinology and Metabolism, Department of Medicine, Virginia Commonwealth University, Richmond (S.B.M.).
authors.forename: Rowena J
authors.initials: RJ
authors.lastname: Dolor
mesh_terms: D000789:Angina, Unstable / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D064887:Observational Studies as Topic; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors
keywords: acute coronary syndrome; proton pump inhibitors