Risk of upper gastrointestinal bleeding associated with non-aspirin cardiovascular drugs, analgesics and nonsteroidal anti-inflammatory drugs :

To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. A case-control study with hospital and community controls. Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. 1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. 144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.

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. 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. 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 (< or = 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 nonsteroidai antiinflammatory drug, the use of a nitrovasodilator or antisecretory therapy was independently associated with a decreased risk of bleeding. The use of nitrovasodilator drugs is independently associated with a decreased risk of upper gastrointestinal bleeding.