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

Am Heart J. 2014 Oct;168(4):495-502.e4. doi: 10.1016/j.ahj.2014.05.017. Epub 2014 Jun 9.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-Ulcer Agents / administration & dosage
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Cardiovascular Diseases / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Follow-Up Studies
  • Incidence
  • Omeprazole / administration & dosage*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / epidemiology
  • Stomach Ulcer / prevention & control*
  • Tablets, Enteric-Coated
  • United States / epidemiology

Substances

  • Anti-Ulcer Agents
  • Platelet Aggregation Inhibitors
  • Tablets, Enteric-Coated
  • Omeprazole
  • Aspirin