A Long-term Prospective Cohort Study of Testing for Helicobacter Pylori and the Long-term Risk of Peptic Ulcer Bleeding With Low-dose Aspirin

Low-dose aspirin (ASA) has emerged as the most important cause of peptic ulcer bleeding worldwide. In western countries, ASA has overtaken NSAIDs as a major cause of peptic ulcer bleeding in the elderly population [1,2]. Management of peptic ulcer bleeding in patients receiving ASA for cardiothrombotic diseases is a clinical dilemma. In a randomized trial of continuous versus interrupted ASA therapy after endoscopic treatment of peptic ulcer bleeding, patients who discontinued ASA had a 10-fold increased incidence of all-cause mortality compared to those who received continuous ASA therapy. On the other hand, patients receiving continuous ASA therapy had a two-fold increased risk of early rebleeding [3]. Thus, preventing the occurrence of peptic ulcer bleeding in ASA users is important in reducing morbidity and mortality.

Emerging evidence from secondary analysis of cardiovascular trials suggests that aspirin also reduces the risk of all cancers, even at cardioprotective doses [4]. With increasing use of ASA for cardiothrombotic diseases and cancer prevention, the global burden of ASA-associated peptic ulcer disease is expected to increase.

A number of risk factors are known to increase the risk of peptic ulcer bleeding with ASA use. These include a history of peptic ulcer or ulcer bleeding, old age, renal failure, concurrent use of ASA and clopidogrel, and Helicobacter pylori (Hp) infection [5-7]. Among these risk factors, concomitant use of clopidogrel and a history of peptic ulcer bleeding and are important predictors of ulcer bleeding with ASA use [7]. On the other hand, Hp is the only risk factor that can be modified. Eradication of Hp therefore offers a hope of reducing the risk of ulcer bleeding in ASA users.

Current European and U.S. guidelines unanimously recommend test-and-treat Hp infection in ASA users who are at risk of ulcer bleeding [8-10]. Despite these guidelines, the long-term benefit of eradicating Hp in high-risk ASA users is uncertain.

In a 6-month randomized trial of ASA users with Hp infection complicated by ulcer bleeding, patients were randomized to one-week of Hp eradication therapy alone or maintenance treatment with omeprazole after ulcers has healed. Our results showed that the incidence of recurrent ulcer bleeding was comparable between the group receiving Hp eradication alone (1.9%) and the group receiving omeprazole (0.9%) [11]. In another 12-month randomized trial, ASA users with Hp infection complicated by ulcer bleeding were randomized to one-week of eradication therapy alone or one week of eradication therapy plus maintenance treatment with lansoprazole. In this study, up to 15% of ASA users developed recurrent ulcer bleeding after eradication of Hp alone. Among the ASA users who developed recurrent ulcer bleeding, however, over two-thirds had failure Hp eradication or used concomitant NSAIDs [12].