ARCH GASTROENTEROHEPATOL 2001: No 20 ( No 3 – 4 ):
We read it for You
Journal: The New England Journal of Medicine
March 29th, 2001 ( New Engl J Med 2001; 344:967-74-9 )
Title: Preventing recurrent upper gastrointestinal
bleeding in patients with Helicobacter pylori
infection who are taking low-dose aspirin or
naproxen
Prevencija ponavljanog proksimalnog
gastrointestinalnog krvarenja u pacijenata sa
Helicobacter pylori infekcijom koji koriste
aspirin u malim dozama ili naproksen
Authors: Chan FL, Chung SSC, Suen BY et others.
Institution: Department of Medicine, Therapeutics and Surgery
Prince of Wales Hospital,
Chinese University of Hong Kong, Hong Kong,. China.
………………. ………………………
ABSTRACT
Background: Many patients who have had upper GI bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steriodal anti-inflammatory drugs (NSAID) 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 GI 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 GI bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80mg of aspirin daily, and those who had been taking other NSAID were given 500mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20mg of omeprazole daily for six months or one week eradication therapy, consisting 120mg bismuth subcitrate, 500mg of tetracycline, and 400mg 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 NSAID. Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9% for patients who received eradication therapy and 0.9% for patients who received omeprazole (absolute difference 1%; 95% confidence interval for the difference, - 1.9 – 3.9%). Among users of other NSAID, the probability of recurrent bleeding was 1.8% for patients receiving eradication therapy and 4.4% for those treated with omeprazole (absolute difference 14.4%; 95% confidence interval for the difference, 4.4 - –4.4%; P=0.005).
Conclusions: Among patients with H.pylori infection and a history with upper GI 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 NSAID, such as naproxen.
……………………………………………………………………………
EDITOR , S DIGEST
Aspirin at low doses and other nesteroidal anti-inflammatory drugs (NSAID) are the major cause of upper GI bleeding. Low dose aspirin is increasingly used for cardiovascular prophylaxis, but it doubles the risk of bleeding ulcers, even at doses as low as 75mg daily. A history of upper GI bleeding due to peptic ulcer is a significant risk factor for recurrent bleeding in those taking low-dose aspirin or other NSAID.
At present there is two strategies that effectively prevent ulcers from bleeding in people who take aspirin or other NSAID and are at high risk for bleeding.
One approach is concurrent therapy with proton pump inhibitors (PPI). It appears that this treatment reduces the risk of ulcer bleeding in patients taking low-dose aspirin or other NSAID.
Another approach is the eradication of H.pylori infection. It is uncertain whether this infection is a risk factor for bleeding ulcers in people who are taking aspirin or other NSAID. Is it not known whether eradicating H.pylori infection would substantially reduce the risk of bleeding ulcers in those taking low-dose aspirin or other NSAID and would thus obviate the need for acid suppressive therapy.
Among persons who are infected with H.pylori and who take aspirin bleeding ulcers could be attributed to H.pylori alone, aspirin or both. It is impossible to distinguish ulcers related to H.pylori from ulcers related to aspirin. In this study published in the New England Journal of Medicine the authors demonstrated that in patients infected with H.pylori who are taking low-dose aspirin, the eradication alone is as effective as maintenance treatment with omeprazole in preventing recurrent upper GI bleeding. This finding suggests that the eradication of H.pylori prevent recurrent bleeding in patients who are taking low-dose aspirin irrespective of the location or cause of ulcers. This may implicate synergistic effect of H.pylori infection and low-dose aspirin in increasing the risk from bleeding from ulcers.
For people who never been treated with nonaspirin NSAID, the same authors already reported that eradication of H.pylori before NSAID treatment was initiated reduces the risk of ulcers. On the contrary, for long-term users of NSAID, however, the eradication of H.pylori has not been shown to prevent GI injury. In this study it is demonstrated that the eradication of H.pylori alone is not sufficient to prevent recurrent GI bleeding from ulcers or erosions.
The divergent outcomes in patients with taking aspirin and those taking other NSAID (naproxen) suggest that H.pylori may have a more important role in ulcer bleeding associated with low-dose aspirin than in bleeding associated with other NSAID. Infection with H.pylori has been shown to impair gastric adaptation with aspirin. The eradication of H.pylori restores this ability and increases the mucosal resistance to aspirin. This enables mucosal barrier to withstand the damaging effects of aspirin. Alternatively, low-dose aspirin may provoke bleeding from preexisting H.pylori – induced ulcers through its antiplatelet effect. This finding implicate that patients who are at risk for bleeding from ulcers and taking low-dose of aspirin should be tested for H.pylori infection and treated if infection is found.
On the contrary to low-dose aspirin, other NSAID can induce more readily peptic ulcers in the absence of H.pylori. This observation is supported by the finding that among users of nonaspirin NSAID who were receiving PPI, those infected with H.pylori have less severe mucosal injury than those who are not infected. This is further supported by the present findings that therapy with omeprazole is superior to the eradication of H.pylori for the secondary prevention in H.pylori- “ positive” ulcers of naproxen (NSAID ).
Vojislav N. Perisic