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

N Engl J Med. 2000 Sep 21;343(12):834-9. doi: 10.1056/NEJM200009213431202.


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 (< 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.

Conclusions: The use of nitrovasodilator drugs is independently associated with a decreased risk of upper gastrointestinal bleeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Aspirin / adverse effects*
  • Case-Control Studies
  • Drug Interactions
  • Drug Therapy, Combination
  • Esophagitis / chemically induced
  • Esophagitis / prevention & control
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / prevention & control*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Nitrates / metabolism
  • Nitrates / therapeutic use*
  • Nitric Oxide / metabolism
  • Odds Ratio
  • Peptic Ulcer Hemorrhage / chemically induced
  • Peptic Ulcer Hemorrhage / prevention & control
  • Risk Factors
  • Vasodilator Agents / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Nitrates
  • Vasodilator Agents
  • Nitric Oxide
  • Aspirin