Based on the most updated publications we have constructed risk ratios estimations and incidence of CV and UGIC events according to the presence of different risk factors, including age and sex. For CV risks we have used Framingham’s 10 year-risk estimations (Wilson, D'Agostino, Levy et al. Circulation 1998) and assumed a 15-20% CV risk reduction with ASA depending on basal risk.

Clopidogrel on top of low-dose ASA reduced that risk a further 8%. For UGIC we assumed a baseline incidence of 1 case per 1000-persons-year and considered the following risk factors: age, male sex, complicated ulcer history, uncomplicated ulcer history, dyspepsia and concomitant use of NSAID use, warfarin/dicumarinics or clopidogrel. We have followed the same methodology and data reported by Hernandez S and Garcia-Rodriguez LA (BMC Medicine 2006, 4:22. doi: 10.1186/1741-7015-4-22).

We have assumed that, 1) low-dose ASA increases the risk of upper gastrointestinal complications by a factor of 2; 2) the risk is constant over time; 3) PPI co-therapy is associated with a 60% GI risk reduction ; 4) H. pylori eradication is associated with another 60% GI risk reduction, but it has been considered only in patients with peptic ulcer history, and its effect added to that obtained with PPI.


Prediction of Coronary Heart Disease using Risk Factor Categories. Wilson, D'Agostino, Levy et al. Circulation. 1998;97:1837-1847.

Association Between Nonsteroidal Anti-inflammatory Drugs and Upper Gastrointestinal Tract Bleeding/Perforation. An Overview of Epidemiologic Studies Published in the 1990s. Hernández-Díaz, S. and García Rodríguez, L.A. Arch Intern Med 2000, 160:2093-2099.

Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. Hernández-Díaz, S. and García Rodríguez, L.A. BMC Medicine 2006, 4:22. doi:10.1186/1741-7015-4-22.

Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. Joseph A. Delaney, Lucie Opatrny, James M. Brophy, Samy Suissa. CMAJ 2007;177(4):347-51.

Low-Dose Acetylsalicylic Acid in Combination With Clopidogrel, Warfarin, Non-Steroidal Anti-Inflammatory Drugs or Steroids: Risk of Upper Gastrointestinal Bleeding. Luis A. Garcia Rodriguez, Kuei-yu Lin, Sonia Hernandez-Diaz, Saga Johansson. Gastroenterology Vol. 138, Issue 5, Supplement 1, Pages S-89-S-90

Patrono C, García Rodríguez LA, Landolfi R, Baigent C: Low-dose Aspirin for the Prevention of Atherothrombosis. N Engl J Med 2005, 353:49-59.

Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet 2009; 373(9678):1849-1860.

Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. N Engl J Med 2006;354:1706-17.

Manuscript091109.doc - Low Dose Aspirin and bleeding-related adverse events: A meta-analysis of randomized trials involving more than 200,000 patients. Angel Lanas, Ping Wu, Edward J. Mills. (submitted for publication)

Preventing recurrent upper gastrointestinal bleeding in patients with helicobacter pylori infection who are taking low-dose aspirin or naproxen. Chan FK, Chung SC, Suen BY, Lee YT, Leung WK, Leung VK, Wu JC, Lau JY, Hui Y, Lai MS, Chan HL, Sung JJ. N Engl J Med, Vol. 344, No. 13.

US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Mar 17;150(6):I-37.

Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD. American Diabetes Association, American Heart Association, American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in people with diabetes. J Am Coll Cardiol. 2010 Jun 22;55(25):2878-86.