By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved two fixed doses of aspirin (ASA) and omeprazole (OMP) for reducing the risk of aspirin-associated gastric ulcers in patients who need aspirin for secondary prevention of cardiovascular and cerebrovascular events. This combination is marketed as Yosprala.
ASA/OMP is indicated for patients who require aspirin for secondary prevention of cardiovascular and cerebrovascular events and who are at risk of aspirin-associated gastric ulcers.1
The recommended dose is one tablet at least 60 minutes before a meal.1 The combination is not interchangeable with the individual components of aspirin and omeprazole.1 ASA/OMP is available as 81 mg and 325 mg delayed-release aspirin and 40 mg of immediate-release omeprazole.
The combination is more effective than enteric-coated aspirin (EC-ASA) in reducing the risk of gastric ulcers with a lower discontinuation rate due to adverse reactions, 7% vs. 11%.1 It provides the convenience of both drugs in one tablet.
ASA/OMP has not been shown to reduce the risk of gastrointestinal bleeding due to aspirin.1
The formulation of ASA/OMP releases omeprazole to raise the gastric pH before releasing aspirin. The efficacy of ASA/OMP was evaluated in two randomized, double-blind trials compared to EC-ASA. Participants presented with a cerebrovascular or cardiovascular diagnosis, were > 55 years of age, had been on aspirin 325 mg for at least three months, and were expected to require ASA for at least six months. Those between 18 and 55 years of age also were required to present with a documented history of gastric or duodenal ulcer within the past five years.
Participants were randomized to ASP/OMP (325 mg/40 mg; n = 524) or EC-ASA 325 mg (n = 525). The primary efficacy endpoint was the incidence of endoscopically determined gastric ulcers. At six months, the incidences were 2.7% and 3.8% for ASA/OMP for the two studies, and 8.5% and 8.7% for EC-ASA, respectively. The cumulative incidence of gastric and/or duodenal ulcers was 3% compared to 12%. In a posthoc analysis, ASA/OMP reduced the risk of subjects with baseline gastric erosions developing gastric ulcers compared to EC-ASA.2 One subject in each group experienced a gastric/duodenal hemorrhage. The most common adverse event was gastritis, and the frequency was similar between the two groups (18% for ASA/OMP, and 16% for EC-ASA). ASA/OMP has not been compared to aspirin nor a proton pump inhibitor or histamine-2 antagonist taken separately, which has been found to be effective in reducing upper gastrointestinal ulcers and bleeding.3,4
The U.S. Preventive Services Task Force recommends low-dose aspirin for the prevention of both cardiovascular-related events and colorectal cancer, mainly in men and women 50-59 years of age who have a ≥ 10% risk of developing cardiovascular disease over 10 years and who are not at increased risk for bleeding.5 However, low-dose aspirin increases the risk of gastroduodenal injury.5,6 Potential risk factors include male gender; elderly (> 70 years of age); having a peptic ulcer; prior gastrointestinal bleed; Helicobacter pylori infection; uncontrolled hypertension; those using antiplatelet drugs, anticoagulants, steroids, or other nonsteroidal anti-inflammatory drugs; and chronic renal failure. The combination of ASA/OMP provides an option to reduce the risk of developing aspirin-associated gastric ulcers in susceptible patients. However, there currently is no evidence that it works any better than aspirin and a proton pump inhibitor taken separately. The projected cost for ASA/OMP is $5 per tablet.
- Yosprala Prescribing Information. Aralez Pharmaceuticals US Inc. September 2016.
- Goldstein JL, Scheiman JM, Fort JG, Whellan DJ. Aspirin use in secondary cardiovascular protection and the development of aspirin-associated erosions and ulcers. J Cardiovasc Pharmacol 2016;68:121-126.
- Mo C, Sun G, Lu ML, et al. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries. World J Gastroenterol 2015;21:5382-5392.
- Chan FK, Kyaw M, Tanigawa T, et al. Similar efficacy of proton-pump inhibitors vs H2-receptor antagonists in reducing risk of upper gastrointestinal bleeding or ulcers in high-risk users of low-dose aspirin. Gastroenterology 2016 Sep 15. pii: S0016-5085(16)35031-4. doi: 10.1053/j.gastro.2016.09.006. [Epub ahead of print].
- American College of Gastroenterology. Low-dose aspirin for 50-to-59-year-olds with cardiovascular disease risk recommended for prevention of colorectal cancer. Available at: . Accessed Oct. 2, 2016.
- Shiotani A, Manabe N, Kamada T, et al. Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: A comprehensive review. J Gastroenterol Hepatol 2012;27(Suppl 3):8-12.