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Previous Volume 343:834-839 September 21, 2000 Number 12 Next

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ABSTRACT

Background The relation between medications that release nitric oxide, such as nitroglycerin and other nitrovasodilators, and upper gastrointestinal bleeding is uncertain. In animals, these medications reduce the gastric damage 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 bleeding in patients taking nitrovasodilators, low-dose aspirin, or other nonsteroidal antiinflammatory drugs. The case group was made up of 1122 consecutive patients admitted to one of four hospitals with bleeding from a peptic lesion. The 2231 control subjects were 1109 patients hospitalized for other reasons and 1122 outpatients from the same geographic area.

Results In the week before admission, 520 (46.3 percent) of the patients with bleeding had taken a nonsteroidal antiinflammatory drug other than low-dose aspirin, 120 (10.7 percent) had taken low-dose aspirin (300 mg per day), 60 (5.3 percent) a nitrovasodilator, and 135 (12.0 percent) an antisecretory agent such as a histamine H₂–receptor antagonist 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 increased risk of bleeding from a peptic ulcer (odds ratio, 7.4; 95 percent confidence interval, 4.5 to 12.0), as was the use of low-dose aspirin alone (odds ratio, 2.4; 95 percent confidence interval, 1.8 to 3.3). The use of a nitrovasodilator was associated with a decreased risk of bleeding (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.9), as was antisecretory therapy (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 0.8). In patients 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.

Source Information

From the Service of Digestive Diseases, University Hospital (A.L., P.S., S.C., R.S.) and the Service of Digestive Diseases, Hospital Miguel Servet (E.B., J.F.), Zaragoza; the Service of Digestive Diseases, Hospital San Jorge, Huesca (J.G., M.M.); and the Service of Digestive Diseases, Hospital San Millán, Logroño (M.S.) — all in Spain.

Address reprint requests to Dr. Lanas at the Servicio de Aparato Digestivo, Hospital Clínico Universitario, 50009 Zaragoza, Spain, or at alanas{at}posta.unizar.es.

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