Gastroprotective Strategy in Aspirin Users

Abstract

343 Aspirin, acetylsalicylic acid, was synthesized by Hoffman of Bayer Laboratories in 1897. Aspirin irreversibly inhibits platelet cyclooxygenase (COX-1) activity, thus preventing the synthesis of thromboxaneA2, and thereby inhibiting platelet aggregation and thrombi formation. A low dose of aspirin, commonly defined as 75–325 mg daily, is effective in preventing cardiovascular (CV) and cerebrovascular disease with decreasing vascular mortality. 1 Meta-analysis data including 142 randomized trials involving approximately 100,000 patients at risk of vascular events showed that aspirin (75– 150 mg/day) reduces by 25% the incidence of ischemic stroke, myocardial infarction, and vascular death when compared with placebo. 2 The efficacy of low-dose aspirin for secondary prevention of CV disease is well documented. However, studies investigating the use of aspirin in primary prevention have produced inconsistent results. The major factor limiting the use of aspirin is concern about the development of gastrointestinal (GI) events, especially GI ulcer and bleeding due to its inhibition of prostaglandin formation in GI mucosa. A study showed that low-dose aspirin (75–325 mg/day) for 3 months was associated with a 7% incidence of endoscopic gastroduodenal ulcer. 3 The use of lowdose aspirin is associated with a 2- to 4-fold increased risk of upper GI (UGI) events. The pooled incidence of major GI bleeding in a meta-analysis of several placebo-controlled trials, using aspirin 75–325 mg daily, was 0.12% per year (95% confidence interval, 0.07– 0.19), with an odds ratio (OR) of 2.07. 4 This means that 833 patients would need to be treated with lowdose aspirin rather than no aspirin to cause an additional episode of major GI bleeding over 1 year. But in high-risk patients who had a past history of aspirinrelated ulcer bleeding, a very high rate of recurrent ulcer bleeding (15%) within 1 year was noted when they continued to take aspirin for cardioprevention after their ulcers had healed and Helicobacter pylori (Hp) had been eradicated. 5 Elderly patients, history of peptic