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J Am Coll Cardiol, 2008; 52:1693-1701, doi:10.1016/j.jacc.2008.08.031
© 2008 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: ACUTE CORONARY SYNDROMES

Impact of Clopidogrel in Patients With Acute Coronary Syndromes Requiring Coronary Artery Bypass Surgery

A Multicenter Analysis

Jeffrey S. Berger, MD, MS*, Carla B. Frye, PharmD{dagger}, Qing Harshaw, MD, PhD{dagger}, Fred H. Edwards, MD{ddagger}, Steven R. Steinhubl, MD§ and Richard C. Becker, MD*,*

* Division of Cardiology, Duke University School of Medicine, Duke Clinical Research Institute; Durham, North Carolina
{dagger} EPI-Q, Inc., Oak Brook, Illinois
{ddagger} Department of Cardiothoracic Surgery, University of Florida, Jacksonville, Florida
§ Department of Cardiovascular Medicine, University of Kentucky, Lexington, Kentucky

Manuscript received April 3, 2008; revised manuscript received June 27, 2008, accepted August 11, 2008.

* Reprint requests and correspondence: Dr. Richard C. Becker, Duke Clinical Research Institute, 2400 Pratt Street, Durham, North Carolina 27705 (Email: richard.becker{at}duke.edu).

Objectives: The purpose of our multicenter study was to examine the impact of pre-operative administration of clopidogrel on reoperation rates, incidence of life-threatening bleeding, inpatient length of stay, and other bleeding-related outcomes in acute coronary syndrome (ACS) patients requiring cardiopulmonary bypass (coronary artery bypass graft surgery [CABG]) in a broad cross section of U.S. hospitals.

Background: There is relative uncertainty about the relationship between clopidogrel and CABG-associated outcomes in the setting of ACS.

Methods: A retrospective cohort analysis was performed of randomly selected ACS patients requiring CABG in 14 hospitals across the U.S. Patients exposed to clopidogrel were compared with those not exposed to clopidogrel within 5 days prior to surgery.

Results: Of the 596 patients enrolled in the study, 298 had been exposed to clopidogrel within 5 days (Group A). Patients in Group A were more than 3-fold more likely to require reoperation for assessment of bleeding than patients not exposed to clopidogrel (6.4% vs. 1.7% Group B, p = 0.004). Major bleeding occurred in 35% of Group A patients versus 26% of Group B patients (p = 0.049). Length of stay was greater in Group A compared with Group B (9.7 ± 6.0 days vs. 8.6 ± 4.7 days, unadjusted p = 0.016). After logistic regression analysis, clopidogrel exposure within 5 days of CABG was the strongest predictor of reoperation (odds ratio [OR]: 4.60, 95% confidence interval [CI]: 1.45 to 14.55) and major bleeding (OR: 1.824, 95% CI: 1.106 to 3.008).

Conclusions: After ACS, patients who undergo CABG within 5 days of receiving clopidogrel are at increased risk for reoperation, major bleeding, and increased length of stay. These risks must be balanced by the clinical benefits of clopidogrel use demonstrated in randomized clinical trials.

Key Words: clopidogrel • coronary artery bypass graft surgery • acute coronary syndrome

Abbreviations and Acronyms
  ACC/AHA = American College of Cardiology/American Heart Association
  ACS = acute coronary syndrome
  CABG = coronary artery bypass graft surgery
  CI = confidence interval
  LOS = length of stay
  OR = odds ratio


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