title: Long-Term Safety of a Coordinated Delivery Tablet of Enteric-Coated Aspirin 325 mg and Immediate-Release Omeprazole 40 mg for Secondary Cardiovascular Disease Prevention in Patients at GI Risk.
abstract: BACKGROUND
  In two, 6-month, randomized, double-blind Phase 3 trials, PA32540 (enteric-coated aspirin 325 mg and immediate-release omeprazole 40 mg) compared to aspirin alone was associated with fewer endoscopic gastric and duodenal ulcers in patients requiring aspirin therapy for secondary cardiovascular disease (CVD) prevention who were at risk for upper gastrointestinal (UGI) events.
  
  
  OBJECTIVE
  In this 12-month, open-label, multicenter Phase 3 study, we evaluated the long-term cardiovascular and gastrointestinal safety of PA32540 in subjects who were taking aspirin 325 mg daily for ≥ 3 months for secondary CVD prevention and were at risk for aspirin-associated UGI events. Enrolled subjects received PA32540 once daily for up to 12 months and were assessed at baseline, month 1, month 6, and month 12.
  
  
  RESULTS
  The overall safety population consisted of 379 subjects, and 290 subjects (76%) were on PA32540 for ≥ 348 days (12-month completers). Adverse events (AEs) caused study withdrawal in 13.5% of subjects, most commonly gastroesophageal reflux disease (1.1%). Treatment-emergent AEs occurred in 76% of the safety population (11% treatment-related) and 73% of 12-month completers (8% treatment-related). The most common treatment-related AE was dyspepsia (2%). One subject had a gastric ulcer observed on for-cause endoscopy. There were five cases of adjudicated nonfatal myocardial infarction, one nonfatal stroke, and one cardiovascular death, but none considered treatment-related.
  
  
  CONCLUSIONS
  Long-term treatment with PA32540 once daily for up to 12 months in subjects at risk for aspirin-associated UGI events is not associated with any new or unexpected safety events.
authors.affiliation: NorthShore University HealthSystem, Evanston, IL, USA.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Goldstein
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.affiliation: University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Scheiman
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Cryer
authors.affiliation: Oregon Health and Science University, Portland, OR, USA.
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: POZEN Inc., Chapel Hill, NC, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Fort
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004304:Dosage Forms; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage*; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D004304:Dosage Forms; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D009853:Omeprazole; D001241:Aspirin
keywords: Aspirin; Dyspepsia; Gastroesophageal reflux disease; Gastrointestinal; Omeprazole; Secondary cardiovascular disease prevention