title: PA32540 (a coordinated-delivery tablet of enteric-coated aspirin 325 mg and immediate-release omeprazole 40 mg) versus enteric-coated aspirin 325 mg alone in subjects at risk for aspirin-associated gastric ulcers: results of two 6-month, phase 3 studies.
abstract: BACKGROUND
  Discontinuations and/or interruptions in aspirin therapy for secondary cardioprotection due to upper gastrointestinal (UGI) complications or symptoms have been shown to increase the risk for subsequent cardiovascular events. PA32540 is a coordinated-delivery, combination tablet consisting of enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg.
  
  
  METHODS
  Two identically-designed, 6-month, randomized, double-blind trials evaluated PA32540 vs. EC-ASA 325 mg in a secondary cardiovascular disease prevention population taking aspirin 325 mg daily for ≥3 months and at risk for ASA-associated gastric ulcers (GUs). The combined study population was 1049 subjects (524 randomized to PA32540, 525 to EC-ASA 325 mg). The primary endpoint was the occurrence of endoscopically-determined gastric ulceration over 6 months. Safety outcomes included the rates of major adverse cardiovascular events (MACE) and UGI symptoms.
  
  
  RESULTS
  Significantly fewer PA32540-treated subjects (3.2%) developed endoscopic GUs vs. EC-ASA 325 mg-treated subjects (8.6%) (P < .001). Overall occurrence of MACE was low (2.1%), with no significant differences between treatments in types or incidence of MACE. PA32540-treated subjects had significantly fewer UGI symptoms (P < .001) and significantly fewer discontinuations due to pre-specified UGI adverse events (1.5% vs. 8.2%, respectively; P < .001).
  
  
  CONCLUSIONS
  PA32540 reduced the incidence of endoscopic GUs compared to EC-ASA 325 mg, but with a similar cardiovascular event profile. Due to fewer UGI symptoms, continuation on aspirin therapy was greater in the PA32540 treatment arm.
authors.affiliation: Thomas Jefferson University, Philadelphia, PA. Electronic address: david.whellan@jefferson.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.affiliation: NorthShore University HealthSystem, Evanston, IL.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Goldstein
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Cryer
authors.affiliation: Oregon Health and Science University, Portland, OR.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Eisen
authors.affiliation: University of Zaragoza, Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.affiliation: University of Florida College of Medicine, Jacksonville, FL.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Miller
authors.affiliation: University of Michigan Medical Center, Ann Arbor, MI.
authors.forename: James M
authors.initials: JM
authors.lastname: Scheiman
authors.affiliation: POZEN, Inc, Chapel Hill, NC.
authors.forename: John G
authors.initials: JG
authors.lastname: Fort
authors.affiliation: POZEN, Inc, Chapel Hill, NC.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Duke University, Durham, NC.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Connor
mesh_terms: D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D015994:Incidence; D009853:Omeprazole / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D013276:Stomach Ulcer / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D013608:Tablets, Enteric-Coated; D014481:United States / Q000453:epidemiology
chemical_list: D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D009853:Omeprazole; D001241:Aspirin