European Heart Journal Advance Access originally published online on April 7, 2009
European Heart Journal 2009 30(12):1457-1466; doi:10.1093/eurheartj/ehp110
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Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial
1 Columbia University Medical Center and Cardiovascular Research Foundation, 161 Fort Washington Avenue, 5th Floor, New York, NY 10032, USA
2 London School of Hygiene and Tropical Medicine, London, UK
3 New York University School of Medicine, New York, NY, USA
4 Emory University School of Medicine, Atlanta, GA, USA
5 Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand
6 San Raffaele Scientific Institute, Milan, Italy
7 Harvard School of Public Health, Boston, MA, USA
8 Duke University School of Medicine, Durham, NC, USA
Received 23 May 2008; revised 16 February 2009; accepted 4 March 2009; online publish-ahead-of-print 7 April 2009.
* Corresponding author. Tel: +1 212 851 9303, Fax: +1 212 851 9300, Email: rmehran{at}crf.org
Aims: To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied.
Methods and Results: A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year.
Conclusion: After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk.
Key Words: Acute coronary syndrome • Myocardial infarction • Mortality • Bleeding • Transfusion
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