Circulation. 2004;110:1202-1208
Published online before print August 16, 2004, doi: 10.1161/01.CIR.0000140675.85342.1B
Published online before print August 16, 2004, doi: 10.1161/01.CIR.0000140675.85342.1B
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(Circulation. 2004;110:1202-1208.)
© 2004 American Heart Association, Inc.
Original Articles |
Benefits and Risks of the Combination of Clopidogrel and Aspirin in Patients Undergoing Surgical Revascularization for Non–ST-Elevation Acute Coronary Syndrome
The Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial
From the Royal Infirmary of Edinburgh, Edinburgh, UK (K.A.A.F.); Division of Cardiology (S.R.M.) and Canadian Cardiovascular Collaboration Project Office (F.Z., S.Y.), Population Health Research Institute, McMaster University, Hamilton, Canada; Academic Medical Center, Amsterdam, Netherlands (R.P.); Baylor Hospital, Houston, Tex (N.L.); and Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minn (B.J.G.).
Correspondence to Professor K.A.A. Fox, Cardiovascular Research, Division of Medical and Radiological Sciences, University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh EH16 4SB UK. E-mail k.a.a.fox{at}ed.ac.uk
Received June 10, 2003; de novo received March 18, 2004; revision received May 26, 2004; accepted June 2, 2004.
Background— Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome, yet all effective therapies also increase the risk of bleeding.
Methods and Results— In the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) trial, 12 562 patients were randomized to clopidogrel or placebo in addition to aspirin, and the primary outcome was cardiovascular (CV) death, myocardial infarction (MI), or stroke. The benefits were consistent among those undergoing percutaneous coronary intervention (PCI) [9.6% for clopidogrel, 13.2% for placebo; relative risk (RR), 0.72; 95% CI, 0.57 to 0.90], coronary artery bypass grafting (CABG) surgery (14.5% for clopidogrel 16.2% for placebo; RR, 0.89; 95% CI, 0.71 to 1.11), and medical therapy only (8.1% for clopidogrel, 10.0% for placebo; RR, 0.80; 95% CI, 0.69 to 0.92; test for interaction among strata, 0.53). For CABG during the initial hospitalization (530 for placebo, 485 for clopidogrel), the frequency of CV death, MI or stroke before CABG was 4.7% for placebo and 2.9% for clopidogrel (RR, 0.56; 95% CI, 0.29 to 1.08). For the entire study, there was a 1% excess of major bleeding but no significant excess of life-threatening bleeding. Among patients undergoing CABG, the rates of life-threatening bleeding were 5.6% for clopidogrel and 4.2% for placebo (RR, 1.30; 95% CI, 0.91 to 1.95; both nonsignificant).
Conclusions— The benefits versus risks of early and long-term clopidogrel therapy (freedom from CV death, MI, stroke, or life-threatening bleeding) are similar in those undergoing revascularization (CABG or PCI) and in the study population as a whole. Overall, the benefits of starting clopidogrel on admission appear to outweigh the risks, even among those who proceed to CABG during the initial hospitalization.
Key Words: clopidogrel • coronary artery bypass • revascularization • coronary disease
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|
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|
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|
|
|
|
 |
|
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|
|
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 |
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 M. S. Sabatine, C. P. Cannon, C. M. Gibson, J. L. Lopez-Sendon, G. Montalescot, P. Theroux, B. S. Lewis, S. A. Murphy, C. H. McCabe, E. Braunwald, et al. Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction Treated With Fibrinolytics: The PCI-CLARITY Study JAMA, September 14, 2005; 294(10): 1224 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Giugliano and E. Braunwald The Year in Non--ST-Segment Elevation Acute Coronary Syndromes J. Am. Coll. Cardiol., September 6, 2005; 46(5): 906 - 919. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 S J Walsh, M S Spence, D Crossman, and A A J Adgey Clopidogrel in non-ST segment elevation acute coronary syndromes: an overview of the submission by the British Cardiac Society and the Royal College of Physicians of London to the National Institute for Clinical Excellence, and beyond Heart, September 1, 2005; 91(9): 1135 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
C. P. Cannon, S. R. Mehta, and S. F. Aranki Balancing the Benefit and Risk of Oral Antiplatelet Agents in Coronary Artery Bypass Surgery Ann. Thorac. Surg., August 1, 2005; 80(2): 768 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hyllner, E. Houltz, and A. Jeppsson Recombinant activated factor VII in the management of life-threatening bleeding in cardiac surgery Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 254 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Gluckman, J. J. Rade, and S. P. Schulman The Value of Clopidogrel Administered Postoperatively Following a Non-ST-Segment Elevation Acute Coronary Syndrome Chest, June 1, 2005; 127(6): 2297 - 2297. [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, S. Silber, P. Albertsson, F. F. Aviles, P. G. Camici, A. Colombo, C. Hamm, E. Jorgensen, J. Marco, J.-E. Nordrehaug, et al. Guidelines for Percutaneous Coronary Interventions: The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology Eur. Heart J., April 2, 2005; 26(8): 804 - 847. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
T. J. Gluckman, M. Sachdev, S. P. Schulman, and R. S. Blumenthal A Simplified Approach to the Management of Non-ST-Segment Elevation Acute Coronary Syndromes JAMA, January 19, 2005; 293(3): 349 - 357. [Abstract] [Full Text] [PDF]
|
|