Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding

Background: The relation between medications that release nitric oxide, suc h as nitroglycerin and other nitrovasodilators, and upper gastrointestinal bleeding is uncertain. In animals, these medications reduce the gastric dam age induced by nonsteroidal antiinflammatory drugs. Nitric oxide, however, inhibits platelet aggregation and may contribute to bleeding from an ulcer. Methods: We performed a case-control study to determine the risk of bleedin g in patients taking nitrovasodilators, low-dose aspirin, or other nonstero idal antiinflammatory drugs. The case group was made up of 1122 consecutive patients admitted to one of four hospitals with bleeding from a peptic les ion. The 2231 control subjects were 1109 patients hospitalized for other re asons and 1122 outpatients from the same geographic area. Results: In the week before admission, 520 (46.3 percent) of the patients w ith bleeding had taken a nonsteroidal antiinflammatory drug other than low- dose aspirin, 120 (10.7 percent) had taken low-dose aspirin (less than or e qual to 300 mg per day), 60 (5.3 percent) a nitrovasodilator, and 135 (12.0 percent) an antisecretory agent such as a histamine H-2-receptor antagonis t or a proton-pump inhibitor. In multivariate models that adjusted for age, sex, and clinical risk factors, the use of a nonsteroidal antiinflammatory drug other than low-dose aspirin was independently associated with an incr eased risk of bleeding from a peptic ulcer (odds ratio, 7.4; 95 percent con fidence interval, 4.5 to 12.0), as was the use of low-dose aspirin alone (o dds ratio, 2.4; 95 percent confidence interval, 1.8 to 3.3). The use of a n itrovasodilator was associated with a decreased risk of bleeding (odds rati o, 0.6; 95 percent confidence interval, 0.4 to 0.9), as was antisecretory t herapy (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.8). In pa tients taking any type of nonsteroidal antiinflammatory drug, the use of a nitrovasodilator or antisecretory therapy was independently associated with a decreased risk of bleeding. Conclusions: The use of nitrovasodilator drugs is independently associated with a decreased risk of upper gastrointestinal bleeding. (N Engl J Med 200 0;343:834-9.) (C) 2000, Massachusetts Medical Society.