Aspirin Combo Aces GI Trials

Abstract

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 were at risk for upper gastrointestinal (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. Study participants were randomized to conventional enteric-coated aspirin at 325 mg/day or to the investigational, once-daily tablet. It 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. He focused on the 215 study participants on aspirin for secondary cerebrovascular-event prevention. The primary study endpoint – the incidence of endoscopically confirmed gastroduodenal ulcers – occurred in 2.0% of patients on the combo tablet, compared with 12.4% of controls on enteric-coated aspirin. 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 tablet, reported Dr. Alberts, director of the stroke program at Northwestern Memorial Hospital, Chicago. The major adverse cardiovascular event rate over 6 months was 2.9% with the combo-tablet 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 an indication in secondary cardiovascular and cerebrovascular prevention in the roughly 15% of patients at risk for aspirin-induced upper GI events. The company has said it wants to make the tablet widely available at an affordable price. Dr. Alberts reported serving as a consultant to Pozen. Editor's NoteThis sounds like a nifty idea, but I'm not sure it's any better than just taking a protein pump inhibitor with aspirin. And PPIs appear to have some significant risks (Clostridium difficile, aspiration pneumonia, hypomagnesemia, and osteoporosis) with long-term use. Plus, 40 mg of omeprazole is a big dose. Still, there will probably be some selected patients who can benefit from this new combo when it gets to market.—Karl Steinberg, MD, CMD,Editor in Chief This sounds like a nifty idea, but I'm not sure it's any better than just taking a protein pump inhibitor with aspirin. And PPIs appear to have some significant risks (Clostridium difficile, aspiration pneumonia, hypomagnesemia, and osteoporosis) with long-term use. Plus, 40 mg of omeprazole is a big dose. Still, there will probably be some selected patients who can benefit from this new combo when it gets to market. —Karl Steinberg, MD, CMD, Editor in Chief