FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 352:238-244 January 20, 2005 Number 3 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Cryer, B. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Concurrent therapy with a proton-pump inhibitor is a standard treatment for patients receiving aspirin who are at risk for ulcer. Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin. We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients.

Methods We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding. After the ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months. The end point was recurrent ulcer bleeding.

Results We enrolled 320 patients (161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole). Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole. The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent (95 percent confidence interval, 4.1 to 13.1 percent) among patients who received clopidogrel and 0.7 percent (95 percent confidence interval, 0 to 2.0 percent) among those who received aspirin plus esomeprazole (difference, 7.9 percentage points; 95 percent confidence interval for the difference, 3.4 to 12.4; P=0.001).

Conclusions Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment, aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding. Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel.

Source Information

From the Departments of Medicine and Therapeutics (F.K.L.C., J.Y.L.C., L.C.T.H., V.W.S.W., A.J.H., J.C.Y.W., W.K.L., Y.T.L., H.L.Y.C., J.J.Y.S.), the School of Pharmacy (V.W.Y.L., K.K.C.L.), and the Departments of Surgery (J.Y.W.L., S.C.S.C.) and Anatomical and Cellular Pathology (K.F.T.), Prince of Wales Hospital, Chinese University of Hong Kong; and the Medical Unit, United Christian Hospital (V.K.S.L., N.N.S.K.) — all in Hong Kong.

Address reprint requests to Dr. Francis K.L. Chan at the Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, 30-32 Ngan Shing St., Shatin, Hong Kong, China, or at fklchan{at}cuhk.edu.hk.

Full Text of this Article

Related Letters:

Clopidogrel versus Aspirin and Esomeprazole to Prevent Recurrent Bleeding
Wolk M. J., Jacobs A. K., Wargo K. A., Baty S. R., Knowles G., Barski P. R. Jr., Chan F. K.L., the Gastrointestinal Research Group
Extract | Full Text | PDF  
N Engl J Med 2005; 352:1716-1718, Apr 21, 2005. Correspondence

This article has been cited by other articles:

• Nikolsky, E., Stone, G. W., Kirtane, A. J., Dangas, G. D., Lansky, A. J., McLaurin, B., Lincoff, A. M., Feit, F., Moses, J. W., Fahy, M., Manoukian, S. V., White, H. D., Ohman, E. M., Bertrand, M. E., Cox, D. A., Mehran, R. (2009). Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors, and clinical implications: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.. J Am Coll Cardiol 54: 1293-1302 [Abstract] [Full Text]  
• Moukarbel, G. V., Signorovitch, J. E., Pfeffer, M. A., McMurray, J. J.V., White, H. D., Maggioni, A. P., Velazquez, E. J., Califf, R. M., Scheiman, J. M., Solomon, S. D. (2009). Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 30: 2226-2232 [Abstract] [Full Text]  
• Seddighzadeh, A., Wolf, A. T., Parasuraman, S., Shetty, R., Vallurupalli, N., Reddy, S., Goldhaber, S. Z. (2009). Gastrointestinal Complications After 3 Months of Dual Antiplatelet Therapy for Drug-eluting Stents as Assessed by Wireless Capsule Endoscopy. CLIN APPL THROMB HEMOST 15: 171-176 [Abstract]  
• Sourgounis, A., Lipiecki, J., Lo, T. S., Hamon, M. (2009). Coronary Stents and Chronic Anticoagulation. Circulation 119: 1682-1688 [Full Text]  
• Hopkins, J., Limacher, M. (2009). The Role of Aspirin in Cardiovascular Disease Prevention in Women. AMERICAN JOURNAL OF LIFESTYLE MEDICINE 3: 123-134 [Abstract]  
• Crea, F., Camici, P. G., De Caterina, R., Lanza, G. A. (2009). CHAPTER 17 Chronic Ischaemic Heart Disease. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full Text]  
• Bhatt, D. L., Scheiman, J., Abraham, N. S., Antman, E. M., Chan, F. K.L., Furberg, C. D., Johnson, D. A., Mahaffey, K. W., Quigley, E. M., Harrington, R. A., Bates, E. R., Bridges, C. R., Eisenberg, M. J., Ferrari, V. A., Hlatky, M. A., Kaul, S., Lindner, J. R., Moliterno, D. J., Mukherjee, D., Schofield, R. S., Rosenson, R. S., Stein, J. H., Weitz, H. H., Wesley, D. J. (2008). ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 52: 1502-1517 [Full Text]  
• Writing Committee Members, , Bhatt, D. L., Scheiman, J., Abraham, N. S., Antman, E. M., Chan, F. K.L., Furberg, C. D., Johnson, D. A., Mahaffey, K. W., Quigley, E. M. (2008). ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 118: 1894-1909 [Full Text]  
• Saini, S. D., Schoenfeld, P., Fendrick, A. M., Scheiman, J. (2008). Cost-effectiveness of Proton Pump Inhibitor Cotherapy in Patients Taking Long-term, Low-Dose Aspirin for Secondary Cardiovascular Prevention. Arch Intern Med 168: 1684-1690 [Abstract] [Full Text]  
• Pignone, M. (2008). Cost-effectiveness of Proton Pump Inhibitor Cotherapy in Patients Taking Long-term, Low-Dose Aspirin for Secondary Cardiovascular Prevention--Invited Commentary. Arch Intern Med 168: 1691-1691 [Full Text]  
• Foley, P., Foley, S., Kinnaird, T., Anderson, R.A. (2008). Clinical review: gastrointestinal bleeding after percutaneous coronary intervention: a deadly combination. QJM 101: 425-433 [Abstract] [Full Text]  
• Sudlow, C (2008). Preventing further vascular events after a stroke or transient ischaemic attack: an update on medical management. PN 8: 141-157 [Abstract] [Full Text]  
• Gellatly, R. M, Ackman, M. L (2008). Single Antiplatelet Therapy for Patients with Previous Gastrointestinal Bleeds. The Annals of Pharmacotherapy 42: 836-840 [Abstract] [Full Text]  
• Patrono, C., Baigent, C., Hirsh, J., Roth, G. (2008). Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 199S-233S [Abstract] [Full Text]  
• Henriksen, P. A., Palmer, K., Boon, N. A. (2008). Management of upper gastrointestinal haemorrhage complicating dual anti-platelet therapy. QJM 101: 261-267 [Abstract] [Full Text]  
• Landolfi, R., Di Gennaro, L. (2008). Prevention of thrombosis in polycythemia vera and essential thrombocythemia. haematol 93: 331-335 [Full Text]  
• Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B. (2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 50: 652-726 [Full Text]  
• Ziegelin, M., Hoschtitzky, A., Dunning, J., Hooper, T. (2007). Does clopidogrel rather than aspirin plus a proton-pump inhibitor reduce the frequency of gastrointestinal complications after cardiac surgery?. ICVTS 6: 534-537 [Abstract] [Full Text]  
• Perez-Gomez, F., Iriarte, J. A., Zumalde, J., Berjon, J., Salvador, A., Alegria, E., Maluenda, M. P., Asenjo, S., Perez-Saldana, R., de la Torre, R. G., Bover, R., Fernandez, C. (2007). Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial. Eur Heart J 28: 996-1003 [Abstract] [Full Text]  
• Hackam, D. G, Eikelboom, J. W (2007). Antithrombotic treatment for peripheral arterial disease. Heart 93: 303-308 [Abstract] [Full Text]  
• Lip, G. Y. H., Karpha, M. (2006). Anticoagulant and Antiplatelet Therapy Use in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: The Need for Consensus and a Management Guideline. Chest 130: 1823-1827 [Abstract] [Full Text]  
• Lanas, A, Garcia-Rodriguez, L A, Arroyo, M T, Gomollon, F, Feu, F, Gonzalez-Perez, A, Zapata, E, Bastida, G, Rodrigo, L, Santolaria, S, Guell, M, de Argila, C M, Quintero, E, Borda, F, Pique, J M, on behalf of the Investigators of the Asociacion E, (2006). Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 55: 1731-1738 [Abstract] [Full Text]  
• Hallas, J., Dall, M., Andries, A., Andersen, B. S., Aalykke, C., Hansen, J. M., Andersen, M., Lassen, A. T. (2006). Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ 333: 726- [Abstract] [Full Text]  
• Hammerman-Rozenberg, R., Jacobs, J. M., Azoulay, D., Stessman, J. (2006). Aspirin prophylaxis and the prevalence of anaemia. Age Ageing 35: 514-517 [Abstract] [Full Text]  
• Greenberger, N. J., Sharma, P. (2006). Update in Gastroenterology and Hepatology. ANN INTERN MED 145: 294-298 [Full Text]  
• Giugliano, R. P., Braunwald, E. (2006). The Year in Non-ST-Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol 48: 386-395 [Full Text]  
• Knight, C. L., Fihn, S. D. (2006). Update in General Internal Medicine. ANN INTERN MED 145: 52-61 [Full Text]  
• Authors/Task Force Members, , Fox, K., Garcia, M. A. A., Ardissino, D., Buszman, P., Camici, P. G., Crea, F., Daly, C., De Backer, G., Hjemdahl, P., Lopez-Sendon, J., Marco, J., Morais, J., Pepper, J., Sechtem, U., Simoons, M., Thygesen, K., ESC Committee for Practice Guidelines (CPG), , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, J., Dean, V., Deckers, J., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J., Zamorano, J. L., Document Reviewers, , Zamorano, J. L, Andreotti, F., Becher, H., Dietz, R., Fraser, A., Gray, H., Antolin, R. A. H., Huber, K., Kremastinos, D. T., Maseri, A., Nesser, H.-J., Pasierski, T., Sigwart, U., Tubaro, M., Weis, M. (2006). Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 27: 1341-1381 [Full Text]  
• Parra, D., Beckey, C., Thomas, T. (2006). Adverse events related to muraglitazar use in diabetes.. JAMA 295: 1997-1998 [Full Text]  
• Vallurupalli, N. G., Goldhaber, S. Z. (2006). Gastrointestinal Complications of Dual Antiplatelet Therapy. Circulation 113: e655-e658 [Full Text]  
• Abrams, J., Thadani, U. (2005). Therapy of Stable Angina Pectoris: The Uncomplicated Patient. Circulation 112: e255-e259 [Full Text]  
• Peterson, W. L (2005). Aspirin plus esomeprazole reduced recurrent ulcer bleeding more than clopidogrel in high risk patients. Evid. Based Med. 10: 112-112 [Full Text]  
• (2005). Drugs to prevent vascular events after stroke. DTB 43: 53-56 [Abstract] [Full Text]  
• (2005). Aspirin + PPI is safer than clopidogrel if patient has history of GI bleeding. BMJ 330: - [Full Text]  
• (2005). JournalScan. Gut 54: 726-726 [Full Text]  
• Wolk, M. J., Jacobs, A. K., Wargo, K. A., Baty, S. R., Knowles, G., Barski, P. R. Jr., Chan, F. K.L., the Gastrointestinal Research Group, (2005). Clopidogrel versus Aspirin and Esomeprazole to Prevent Recurrent Bleeding. NEJM 352: 1716-1718 [Full Text]  
• Malik, I. (2005). JournalScan. Heart 91: 559-560 [Full Text]  
• (2005). Which Strategy for Patients at Risk for Aspirin-Related Ulcer Bleeding?. Journal Watch Cardiology 2005: 5-5 [Full Text]  
• (2005). Aspirin/Esomeprazole vs. Clopidogrel for Patients with Aspirin-Related Bleeding Ulcers. JWatch General 2005: 1-1 [Full Text]  
• Cryer, B. (2005). Reducing the Risks of Gastrointestinal Bleeding with Antiplatelet Therapies. NEJM 352: 287-289 [Full Text]  
• Harrison, C. N. (2005). Platelets and Thrombosis in Myeloproliferative Diseases. ASH Education Book 2005: 409-415 [Abstract] [Full Text]