Prevention of Recurrent Ulcer Bleeding in High-risk Aspirin Users Who Are Not Infected With Helicobacter Pylori

Low-dose aspirin is increasingly used for the prophylaxis against coronary heart disease and stroke. However, it is also an important cause of peptic ulcer bleeding worldwide. In England and Wales, low-dose aspirin is estimated to account for about 10% of ulcer bleeding in people aged 60 and over [Weil 1995]. The problem of aspirin-related ulcer disease is expanding with the increasing use of aspirin for cardiovascular prophylaxis.

No dose of aspirin is entirely free of risk. Using a daily dose of aspirin as low as 75 mg, the risk of ulcer bleeding doubles that of non-users [Weil 1995]. Previous ulcer disease and concurrent major medical illnesses are important risk factors for ulcer bleeding with low-dose aspirin. Among aspirin users, those with previous ulcer disease have a 5-fold increased risk of ulcer bleeding [Lanas 2000].

Various strategies have been used to prevent recurrent ulcer bleeding in high-risk aspirin users, such as eradication of Helicobacter pylori, the use of prophylactic anti-ulcer drugs or enteric-coated aspirin. Recently, the investigators have shown that the eradication of H. pylori is comparable to maintenance treatment with omeprazole, a potent acid suppressant, in preventing recurrent ulcer bleeding for high-risk aspirin users [Chan 2001]. However, about 50% of aspirin users are not infected with H. pylori.

The optimal strategy to prevent ulcer complications for high-risk aspirin users who are not infected with H. pylori remains undefined. Although co-therapy of aspirin with an acid suppressant reduces the risk of ulcer bleeding, drug compliance may limit its clinical usefulness particularly in patients who are already receiving multiple drugs.

High risk cohort:

Inclusion criteria

• History of endoscopically confirmed ulcer bleeding
• Need long-term aspirin for cardiovascular or cerebrovascular prophylaxis
• A negative test for H. pylori based on histology

Exclusion criteria

• Concomitant use of anti-ulcer drug, anticoagulant, non-aspirin NSAIDs or steroids
• Current or past H. pylori infection
• Previous acid-reduction gastric surgery
• Gastric outlet obstruction, erosive esophagitis, gastroesophageal varices
• Moribund or incurable cancers

Average-risk cohort

Inclusion criteria

Patients must fulfill ALL of the following:

• No history of ulcer bleeding
• Need long-term aspirin for cardiovascular or cerebrovascular prophylaxis
• H. pylori positive OR negative

Exclusion criteria

• Concomitant use of anti-ulcer drug, anticoagulant, non-aspirin NSAIDs or steroid
• Previous acid-reduction gastric surgery
• Moribund or incurable cancers
• Previous attempts of H. pylori eradication