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CLINICAL RESEARCH STUDY

Long-Term Use of Aspirin and the Risk of Gastrointestinal Bleeding
Edward S. Huang, MD, MPH,a Lisa L. Strate, MD, MPH,b Wendy W. Ho, MD, MPH,c Salina S. Lee, MD,d Andrew T. Chan, MD, MPHa,e
a

Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston; bDivision of Gastroenterology, Department of Medicine, University of Washington,Seattle; cDivision of Digestive Diseases, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles; dDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; e Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

ABSTRACT BACKGROUND: In short-term trials, aspirin is associated withgastrointestinal bleeding. However, the effect of dose and duration of aspirin use on risk remains unclear. METHODS: We conducted a prospective study of 87,680 women enrolled in the Nurses’ Health Study in 1990 who provided biennial data on aspirin use. We examined the relative risk (RR) of major gastrointestinal bleeding requiring hospitalization or blood transfusion. RESULTS: During a 24-yearfollow-up, 1537 women reported a major gastrointestinal bleeding. Among women who used aspirin regularly ( 2 standard [325 mg] tablets/week), the multivariate RR of gastrointestinal bleeding was 1.43 (95% confidence interval [CI], 1.29-1.59) when compared with nonregular users. Compared with women who denied any aspirin use, the multivariate RRs of gastrointestinal bleeding were 1.03 (95% CI, 0.85-1.24)for women who used 0.5 to 1.5 standard aspirin tablets/week, 1.30 (95% CI, 1.07-1.58) for women who used 2 to 5 tablets/week, 1.77 (95% CI, 1.44-2.18) for women who used 6 to 14 tablets/week, and 2.24 (95% CI, 1.66-3.03) for women who used more than 14 tablets/week (Ptrend .001). Similar dose-response relationships were observed among short-term users ( 5 years; Ptrend .001) and long-term users (5 years; Ptrend .001). In contrast, after adjustments were made for dose, increasing duration of use did not confer a greater risk of bleeding (Ptrend .28). CONCLUSION: Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowesteffective dose among both short- and long-term users. © 2011 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2011) 124, 426-433 KEYWORDS: Aspirin; Dose; Duration; Gastrointestinal bleeding; Long-term

Funding: Supported by grants (CA 87969, CA 55075, CA 107412, CA 137178) from the National Cancer Institute, National Institutes of Health. Dr. Chan was a recipient of the AmericanGastroenterological Association/Foundation for Digestive Health and Nutrition Pilot Research Award for this work. Dr. Chan is a Damon Runyon Clinical Investigator. Dr. Huang is supported by American Gastroenterological Association Fellow to Faculty Transition Award. No pharmaceutical industry funds were received for preparation of this manuscript. The National Cancer Institute, the NationalInstitutes of Health, the American Gastroenterological Association, the Foundation for Digestive Health and Nutrition, and the Damon Runyon Cancer Research Foundation had no role in the collection, management, analysis, or interpretation of the data, and had no role in the preparation, review, or approval of the manuscript. Conflict of Interest: Dr. Chan has served as a consultant to Bayer HealthCare.Authorship: All authors had access to the data and played a role in writing this manuscript: study concept and design (ESH, WWH, ATC); acquisition of data (ESH, WWH, SSL, ATC); analysis and interpretation of data (ESH, LLS, ATC); drafting of the manuscript (ESH, LLS, WWH, SSL, ATC); critical revision of the manuscript for important intellectual content (ESH, LLS, WWH, SSL, ATC); statistical...