title: Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.
abstract: BACKGROUND
  The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin.
  
  
  OBJECTIVE
  The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets.
  
  
  METHODS
  Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists.
  
  
  RESULTS
  Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group.
  
  
  CONCLUSIONS
  Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. Electronic address: dlbhattmd@post.harvard.edu.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: University of Texas Southwestern and Veterans Affairs North Texas Health Care System, Dallas, Texas.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Cryer
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Department of Biostatistics, Boston University, Boston, Massachusetts.
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Hsieh
authors.affiliation: Harvard Clinical Research Institute, Boston, Massachusetts; Department of Biostatistics, Boston University, Boston, Massachusetts.
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Doros
authors.affiliation: Newark Beth Israel Medical Center, Newark, New Jersey.
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, Illinois.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schnitzer
authors.affiliation: Parexel International, Waltham, Massachusetts.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Shook
authors.affiliation: Lexicon Pharmaceuticals, Basking Ridge, New Jersey.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapuerta
authors.affiliation: Constellation Pharmaceuticals, Cambridge, Massachusetts.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Goldsmith
authors.affiliation: Yale School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Loren
authors.initials: L
authors.lastname: Laine
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts; Harvard Clinical Research Institute, Boston, Massachusetts.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004415:Dyspepsia / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007415:Intestinal Obstruction / Q000139:chemically induced / Q000517:prevention & control; D007416:Intestinal Perforation / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D009853:Omeprazole / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin
keywords: bleeding; clinical outcomes; clinical trials; coronary artery disease