HONOLULU – A novel proprietary combination of aspirin and immediate-release omeprazole in a coordinated-delivery tablet resulted in markedly fewer gastroduodenal ulcers and treatment discontinuations than conventional enteric-coated aspirin in patients on antiplatelet therapy for secondary prevention of cerebrovascular events.
Two double-blind, 6-month, randomized phase III clinical trials totaling 1,049 patients with an indication for daily aspirin for secondary cardiovascular or cerebrovascular prevention included 215 subjects with prior ischemic stroke or transient ischemic attack (TIA). All participants in the phase III trials were at risk for upper GI ulcers by virtue of being at least 55 years of age or having a documented history of gastric or duodenal ulcer within 5 years prior to enrollment. Baseline endoscopy was negative in all subjects.
Dr. Mark J. Alberts
Study participants were randomized to conventional enteric-coated aspirin at 325 mg/day or to the investigational tablet, known for now as PA32540. This once-daily tablet contains 40 mg of immediate-release omeprazole layered around 325 mg of pH-sensitive aspirin, Dr. Mark J. Alberts explained at the International Stroke Conference sponsored by the American Heart Association.
He focused on the 215 study participants on aspirin for secondary cerebrovascular prevention. The primary study endpoint – the incidence of endoscopically confirmed gastroduodenal ulcers – occurred in 2.0% of patients on PA32540, compared with 12.4% of controls on enteric-coated aspirin.
Moreover, discontinuation of therapy due to dyspepsia, erosive gastritis, or other prespecified upper GI events occurred in 8% of controls and in none of the participants on the combo tablet, reported Dr. Alberts, professor of neurology at Northwestern University, Chicago, and director of the stroke program at Northwestern Memorial Hospital.
The major adverse cardiovascular event rate over the course of 6 months was 2.9% in the PA32540 group and 4.4% with enteric-coated aspirin, a nonsignificant difference.
These study findings support the hypothesis that a single tablet formulation of aspirin and GI-protective omeprazole may safely improve long-term compliance with aspirin therapy in patients at increased risk for upper GI toxicity, Dr. Alberts observed.
Pozen, which sponsored the phase III trials, has announced it will seek regulatory approval of the coordinated-delivery product with an indication for use in secondary cardiovascular and cerebrovascular prevention in the roughly 15% of patients at risk for aspirin-induced upper GI adverse events. The company is currently seeking strategic partners to help market the novel product on a wide scale at an affordable price after PA32540 receives regulatory approval.
Dr. Alberts reported serving as a consultant to Pozen.