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CLINICAL RESEARCH: ACUTE CORONARY SYNDROMES

Outcomes Following Pre-Operative Clopidogrel Administration in Patients With Acute Coronary Syndromes Undergoing Coronary Artery Bypass Surgery

The ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial

Ramin Ebrahimi, MD^_*,_*, Cornelius Dyke, MD, Roxana Mehran, MD, Steven V. Manoukian, MD, Frederick Feit, MD^||, David A. Cox, MD^¶, Bernard J. Gersh, MB, ChB, DPhil^#, E. Magnus Ohman, MD^_**, Harvey D. White, MD, Jeffrey W. Moses, MD, James H. Ware, PhD, A. Michael Lincoff, MD and Gregg W. Stone, MD

^_* University of California Los Angeles and the Greater Los Angeles VA Medical Center, Los Angeles, California
Gaston Memorial Hospital, Gastonia, North Carolina
Columbia University Medical Center and The Cardiovascular Research Foundation, New York, New York
The Sarah Cannon Research Institute and The Centennial Heart Center, Nashville, Tennessee
^|| New York University School of Medicine, New York, New York
^¶ Lehigh Valley Hospital, Allentown, Pennsylvania
^# Mayo Clinic, Rochester, Minnesota
^_** Duke University Medical Center, Durham, North Carolina
Auckland City Hospital, Auckland, New Zealand
Harvard University, Boston, Massachusetts
Cleveland Clinic Foundation, Cleveland, Ohio

Manuscript received December 9, 2008; revised manuscript received February 23, 2009, accepted March 3, 2009.

^_* Reprint requests and correspondence: Dr. Ramin Ebrahimi, Greater Los Angeles VA Medical Center, Department of Medicine, Cardiology Section (111E), 11301 Wilshire Boulevard, Los Angeles, California 90073 (Email: ebrahimi{at}UCLA.edu).

Objectives: This study sought to evaluate the impact of upstream clopidogrel in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) requiring coronary artery bypass grafting (CABG) from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial.

Background: Despite benefits of clopidogrel in patients with NSTE-ACS undergoing percutaneous coronary intervention, this agent is often not administered upstream (before angiography) as recommended by the American College of Cardiology/American Heart Association guidelines because of potential bleeding in the minority of patients who require CABG.

Methods: The ACUITY trial enrolled 13,819 patients with NSTE-ACS undergoing early invasive management. The timing of clopidogrel initiation was per investigator discretion. A 5-day washout period before CABG was recommended for patients having received clopidogrel.

Results: Of 13,819 patients enrolled, 1,539 (11.1%) underwent CABG before discharge. Clopidogrel-exposed patients had a longer median duration of hospitalization (12.0 days vs. 8.9 days, p < 0.0001), but fewer adverse composite ischemic events (death, myocardial infarction, or unplanned revascularization) at 30 days; 12.7% vs. 17.3%, p = 0.01), with nonsignificantly different rates of non–CABG-related major bleeding (3.4% vs. 3.2%, p = 0.87) and post-CABG major bleeding (50.3% vs. 50.9%, p = 0.83) compared with those patients not administered clopidogrel. By multivariable analysis, clopidogrel use before CABG was an independent predictor of reduced 30-day composite ischemia (odds ratio: 0.67, 95% confidence interval: 0.48 to 0.92, p = 0.001) but not of increased post-CABG major bleeding (odds ratio: 0.98, 95% confidence interval: 0.80 to 1.19, p = 0.80).

Conclusions: Clopidogrel administration before catheterization in patients with NSTE-ACS requiring CABG is associated with significantly fewer 30-day adverse ischemic events without significantly increasing major bleeding, compared to withholding clopidogrel until after angiography. These findings support the American College of Cardiology/American Heart Association guidelines for upstream clopidogrel administration in all NSTE-ACS patients, including those who subsequently undergo CABG. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158 [ClinicalTrials.gov] ).

Key Words: coronary artery bypass surgery • clopidogrel • acute coronary syndromes

Abbreviations and Acronyms   ACC = American College of Cardiology   ACS = acute coronary syndromes   AHA = American Heart Association   CABG = coronary artery bypass grafting   CI = confidence interval   CPK = creatine phosphokinase   GP = glycoprotein   MI = myocardial infarction   NACE = net adverse clinical events   NSTE = non–ST-segment elevation   NSTEMI = non–ST-segment elevation myocardial infarction   OR = odds ratio   PCI = percutaneous coronary intervention   STS = Society of Thoracic Surgeons   UFH = unfractionated heparin   ULN = upper limit of normal

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