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EXPEDITED REVIEW

Impact of Major Bleeding on 30-Day Mortality and Clinical Outcomes in Patients With Acute Coronary Syndromes

An Analysis From the ACUITY Trial

Steven V. Manoukian, MD, FACC^_*,_*, Frederick Feit, MD, FACC, Roxana Mehran, MD, FACC, Michele D. Voeltz, MD^_*, Ramin Ebrahimi, MD, FACC, Martial Hamon, MD^||, George D. Dangas, MD, PhD, FACC, A. Michael Lincoff, MD, FACC^¶, Harvey D. White, DSc, FACC^#, Jeffrey W. Moses, MD, FACC, Spencer B. King, MD, MACC^_**, E. Magnus Ohman, MD, FACC and Gregg W. Stone, MD, FACC

^_* Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
^_** Fuqua Heart Center, Atlanta, Georgia
Department of Medicine, New York University School of Medicine, New York, New York
Department of Medicine, Columbia University Medical Center and the Cardiovascular Research Foundation, New York, New York
Department of Medicine, University of California Los Angeles, Los Angeles, California
^|| Service des Maladies du Cur et des Vaisseaux, Centre Hospitalier Universitaire de Caen, Caen, France
^¶ Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
^# Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand
Department of Medicine, Duke University School of Medicine, Durham, North Carolina

Manuscript received February 10, 2007; revised manuscript received February 26, 2007, accepted February 26, 2007.

^_* Reprint requests and correspondence: Dr. Steven V. Manoukian, Emory University School of Medicine, Emory Crawford Long Hospital, 550 Peachtree Street, MOT, 6th Floor, Cardiology, Atlanta, Georgia 30308 (Email: steven.manoukian{at}emory.edu).

Objectives: The purpose of this study was to determine the predictors of major bleeding and the impact of major bleeding on outcomes, including mortality, in acute coronary syndromes (ACS).

Background: Whether major bleeding independently predicts mortality in patients with ACS undergoing an early invasive strategy is undefined.

Methods: Patients (n = 13,819) with moderate- and high-risk ACS were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy (plus provisional GPI). Logistic regression was used to determine predictors of 30-day major bleeding and mortality.

Results: Major bleeding rates in patients treated with heparin plus GPI were higher versus bivalirudin monotherapy (5.7% vs. 3.0%, p < 0.001) and similar versus bivalirudin plus GPI (5.7% vs. 5.3%, p = 0.38). Independent predictors of major bleeding were advanced age, female gender, diabetes, hypertension, renal insufficiency, anemia, no prior percutaneous coronary intervention, cardiac biomarker elevation, ST-segment deviation 1 mm, and treatment with heparin plus GPI versus bivalirudin monotherapy. Patients with major bleeding had higher 30-day rates of mortality (7.3% vs. 1.2%, p < 0.0001), composite ischemia (23.1% vs. 6.8%, p < 0.0001), and stent thrombosis (3.4% vs. 0.6%, p < 0.0001) versus those without major bleeding. Major bleeding was an independent predictor of 30-day mortality (odds ratio 7.55, 95% confidence interval 4.68 to 12.18, p < 0.0001).

Conclusions: Major bleeding is a powerful independent predictor of 30-day mortality in patients with ACS managed invasively. Several factors independently predict major bleeding, including treatment with heparin plus GPI compared with bivalirudin monotherapy. Knowledge of these findings might be useful to reduce bleeding risk and improve outcomes in ACS.

Abbreviations and Acronyms   ACS = acute coronary syndromes   CABG = coronary artery bypass graft surgery   GRACE = Global Registry of Acute Coronary Events   GPI = glycoprotein IIb/IIIa inhibitor/inhibition   MI = myocardial infarction   PCI = percutaneous coronary intervention

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