title: Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial.
abstract: BACKGROUND
  Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention.
  
  
  METHODS
  All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up.
  
  
  RESULTS
  Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P = .02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P = .05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P = .27).
  
  
  CONCLUSIONS
  PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Mass.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Mass; Harvard Clinical Research Institute, Boston, Mass.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: University of Texas Southwestern and Veterans Affairs North Texas Health Care System, Dallas.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Cryer
authors.affiliation: Harvard Clinical Research Institute, Boston, Mass; Department of Biostatistics, Boston University, Mass.
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Harvard Clinical Research Institute, Boston, Mass.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Hsieh
authors.affiliation: Harvard Clinical Research Institute, Boston, Mass; Department of Biostatistics, Boston University, Mass.
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.affiliation: Newark Beth Israel Medical Center, NJ.
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.affiliation: University of Zaragoza, Instituto de Investigación Sanitaria Aragón, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.affiliation: Departments of Physical Medicine and Rehabilitation and Internal Medicine-Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnitzer
authors.affiliation: PAREXEL International, Waltham, Mass.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Shook
authors.affiliation: Lexicon Pharmaceuticals, Basking Ridge, NJ.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapuerta
authors.affiliation: Constellation Pharmaceuticals, Cambridge, Mass.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Goldsmith
authors.affiliation: Yale School of Medicine, New Haven, Conn; VA Connecticut Healthcare System, West Haven, Conn.
authors.forename: Loren
authors.initials: L
authors.lastname: Laine
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Mass. Electronic address: dlbhattmd@post.harvard.edu.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control*; D006801:Humans; D009853:Omeprazole / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000379:methods* / Q000706:statistics & numerical data; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin
keywords: Acute coronary syndrome; Bleeding; Clinical outcomes; Clinical trials; Coronary artery disease; Percutaneous coronary intervention; Proton-pump inhibitors