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

Abstract

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.

Figure 1

Observed and expected risk of mortality within 1 year by risk group. The comparison of the observed and expected probabilities of dying demonstrates the model's goodness of fit.

Figure 2

Cumulative risk of (i) death; (ii) recurrent MI, (iii) major bleed; (iv) non-CABG related transfusion. The cumulative risk of mortality (to 1 year), recurrent MI, major bleed, and non-CABG related transfusion (to 35 days).

Figure 3

Influence of recurrent MI, major bleed, and non-CABG related blood transfusion on mortality to 1 year [three Cox model with MIs, bleeds, and transfusions as time-updated covariates (pre-/post-event) adjusted for baseline predictors]. When included as a time-updated covariate in the Cox model, major bleeding and blood transfusion within 30 days of randomization had similar or slightly greater risk of 1-year mortality compared with MI within 30 days.

Figure 4

Influence of recurrent MI, major bleed, and non-CABG related transfusion on mortality to 1 year [three Cox model with recurrent MI, major bleed, and transfusion as binary time-updated covariates (time since event) adjusted for baseline predictors]. The excess risk of death following a major bleed and transfusion within 30 days of randomization remained steady and highly significant over time, whereas the impact of an MI within 30 days on the risk of mortality decreased rapidly over time.