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(Circulation. 2006;114:774-782.)
© 2006 American Heart Association, Inc.

Coronary Heart Disease

Adverse Impact of Bleeding on Prognosis in Patients With Acute Coronary Syndromes

John W. Eikelboom, MBBS, MSc; Shamir R. Mehta, MD, MSc; Sonia S. Anand, MD, PhD; Changchun Xie, PhD; Keith A.A. Fox, MBChB; Salim Yusuf, MBBS, DPhil

From the Thrombosis Service (J.W.E.) and Population Health Research Institute (J.W.E., S.R.M., S.S.A., C.X., S.Y.), Hamilton Health Sciences, Hamilton, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada (J.W.E., S.R.M., S.S.A., S.Y.); and University and the Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK (K.A.A.F.).

Correspondence to John Eikelboom, Thrombosis Service, Hamilton General Hospital, 237 Barton St East, Hamilton, Ontario L8L 2X2, Canada. E-mail eikelbj{at}mcmaster.ca

Received January 7, 2006; revision received June 21, 2006; accepted June 22, 2006.

Background— The use of multiple antithrombotic drugs and aggressive invasive strategies has increased the risk of major bleeding in acute coronary syndrome (ACS) patients. It is not known to what extent bleeding determines clinical outcome.

Methods and Results— Using Cox proportional-hazards modeling, we examined the association between bleeding and death or ischemic events in 34 146 patients with ACS enrolled in the Organization to Assess Ischemic Syndromes and the Clopidogrel in Unstable Angina to Prevent Recurrent Events studies. Patients with major bleeding were older, more often had diabetes or a history of stroke, had a lower blood pressure and higher serum creatinine, more often had ST-segment changes on the presenting ECG, and had a 5-fold-higher incidence of death during the first 30 days (12.8% versus 2.5%; P<0.0001) and a 1.5-fold-higher incidence of death between 30 days and 6 months (4.6% versus 2.9%; P=0.002). Major bleeding was independently associated with an increased hazard of death during the first 30 days (hazard ratio, 5.37; 95% CI, 3.97 to 7.26; P<0.0001), but the hazard was much weaker after 30 days (hazard ratio, 1.54; 95% CI, 1.01 to 2.36; P=0.047). The association was consistent across subgroups according to cointerventions during hospitalization, and there was an increasing risk of death with increasing severity of bleeding (minor less than major less than life-threatening; P for trend=0.0009). A similar association was evident between major bleeding and ischemic events, including myocardial infarction and stroke.

Conclusions— In ACS patients without persistent ST-segment elevation, there is a strong, consistent, temporal, and dose-related association between bleeding and death. These data should lead to greater awareness of the prognostic importance of bleeding in ACS and should prompt evaluation of strategies to reduce bleeding and thereby improve clinical outcomes.

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