Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen

N Engl J Med. 2001 Mar 29;344(13):967-73. doi: 10.1056/NEJM200103293441304.


Background: Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients.

Methods: We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months.

Results: We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005).

Conclusions: Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Anti-Ulcer Agents / therapeutic use*
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Drug Therapy, Combination
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / complications
  • Gastrointestinal Hemorrhage / prevention & control*
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori*
  • Humans
  • Metronidazole / therapeutic use
  • Naproxen / adverse effects
  • Naproxen / therapeutic use
  • Omeprazole / therapeutic use*
  • Organometallic Compounds / therapeutic use
  • Secondary Prevention
  • Tetracycline / therapeutic use


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • Organometallic Compounds
  • Metronidazole
  • Naproxen
  • Tetracycline
  • bismuth tripotassium dicitrate
  • Omeprazole
  • Aspirin