Aspirin Dose Linked to Risk of Upper GI Bleeding

The study by Huang et al. provides further evidence that use of aspirin increases the risk of major GI bleeding and that this risk increases with increasing dose of aspirin. Meta analysis of randomized trials of low-dose aspirin (75-325 mg daily)for cardiovascular prophylaxis indicates approximately a 2-fold increase in major GI bleeding, similar to the results of this analysis.

In addition, increasing the dose above 325 mg daily also has been shown to significantly increase the risk of bleeding. Since regular use of low-dose aspirin provides approximately100% inhibition of cyclooxygenase-1 and thromboxane, the increased risk of upper GI bleeding with higher-dose aspirin presumably relates to increased mucosal injury (likely due to greater cyclooxygenase-2 inhibition).

This study did not show a significant risk of 325 mg of aspirin taken 2-5 times per week. However,prior large randomized controlled trials have documented a significant increase in major GI bleeding even when low-dose aspirinis taken every other day.The statement that longer duration of use was not significantly associated with an increased risk of upper GI bleeding should not be taken to suggest that risk does not continue with longer-term use of aspirin. Prospective randomized trials of aspirin and other NSAIDs document that the cumulative incidence of GI complications continues to increase over time. Despite the GI risk, patients with established cardiovascular disease clearly benefit from the use of low-dose aspirin and, in general, this benefit out weighs the risk of GI bleeding. Current consensus recommendations from cardiology and GI organizations state that the GI risk needs to be determined in individual patients, and if low-dose aspirin is required in patients with increased GI risk, then cotherapy is recommended.

LOREN A. LAINE, M.D., AGAF,is Professor of Medicine, KeckSchool of Medicine, University of Southern California, Los Angeles,and is Vice President of the AGAInstitute. P E


Aspirin Dose Linked to Risk of Upper GI Bleeding

BY HEIDI SPLETEE
lsevier Global Medical News SAN ANTONIO –

Men who took more than 14 aspirin per week were more than twice as likely to report upper gastrointestinal bleeding as were men who reported no aspirin use, but increased duration of use did not appear to raise the risk of GI bleeding, said Dr. EdwardHuang at the annual meeting of the American College of Gastroenterology.

Evidence regarding the impact of aspirin use on GI bleeding is conflicting because of the limitations of previous studies, said Dr. Huang ofMassachusetts General Hospital in Boston.

To examine the long-term effects of aspirin dose and duration on GI bleeding, Dr.Huang and his colleagues conducted a prospective study of32,989 participants in the Health Professionals Follow up Study, a longitudinal studyof male health professionals in the United States. In 2006 and 2008, participants were asked to report any past episodes of GI bleeding severe enough to require hospitalization or blood transfusion.

The average age of the men when they enrolled in the study was 60 years, and those with a history of peptic ulcer disease were excluded. During a mean 14-year follow-up period, 707 men had an episode of major GI bleeding. After adjustment for risk factors including use of NSAIDs, age, smoking, exercise ,and body mass index, the risk ratios for upper GI bleeding were 1.05 (95% confidence interval [CI], 0.71-1.52) for men who took 0.5-1.5 standard(325 mg) aspirin tablets per week, 1.31 (95% CI, 0.88-1.95) for those who took 2-5 tablets per week, 1.63 (95%CI, 1.15-2.32) for those who took 6-14 tablets per week, and 2.40 (95% CI, 1.10-5.22) for those who took more than 14 tablets per week, compared with men who reported no aspirin use (P less than .001). Short-term aspirin use was defined as less than 5 years, and long-term use was defined as 5 years or longer.

“The dose-response relationship is significant regardless of duration of use,” Dr. Huang noted. By contrast, longer duration of use was not significantly associated with an increased risk of upper GI bleeding, Dr.Huang said. However, individuals who use aspirin the longest tend to use the highest dose, he added.

Dr. Neena S. Abraham said in an interview, “This longitudinal study re-iterates the importance of a high-average daily dose of aspirin as an independent risk factor for subsequent upper gastrointestinal hemorrhage, and helps debunk the clinical myth that duration of treatment is the only relevant risk factor.”“Not only is this study consistent with other longitudinal studies, such as theNurses Heath Study, it complements observationa lstudies that have shown a substantial dose-response relationship between aspirin and the risk of GI bleeding,”said Dr. Abraham, a gastroenterologistat the Michael E. DeBakey VA Medical Center and associate professor of medicine at Baylor College of Medicine,both in Houston.“Given this data, gastroenterologists should re-double their efforts to educate both patients and their providers that the best dose of aspirin is the lowest possible dose for the clinical indication being treated,” she added.

The results suggest that both short term and long-term aspirin users can minimize the risk of upper GI bleeding by using the lowest effective dose, Dr.Huang said.Dr. Huang had no financial conflicts to disclose.