Causality analysis of the relationship between bleeding and lethality in Acute Coronary Syndromes

Hemorrhagic events in Acute Coronary Syndromes (ACS) have been independently associated with death in international multicenter registries. However, that association has not been tested in Brazil and the true causal relationship between bleeding and death has not been completely shown.

To test the following hypotheses: (1) major bleeding is an independent predictor of in-hospital death in ACS; (2) the relationship between those two endpoints is causal.

This study included patients meeting predefined criteria of unstable angina, non-ST-segment elevation myocardial infarction or ST-segment elevation myocardial infarction. Major bleeding during hospitalization was defined according to the Bleeding Academic Research Consortium (types 3 or 5). Logistic regression and analysis of the sequence of events were used to assess the association between bleeding and death.

Of the 455 patients studied, 29 experienced major bleeding (6.4%; 95% CI = 4.3-9.0%). They had in-hospital mortality of 21%, as compared with 5.6% of those not experiencing bleeding (RR = 4.0; 95% CI = 1.8-9.1; P = 0.001). After adjusting for the propensity score, major bleeding remained as a predictor of in-hospital death (OR = 3.34; 95% CI = 1.2-9.5; P = 0.02). Of the 29 patients who experienced bleeding, six died. However, the detailed analysis of the sequence of events showed causal relationship only in one case.

(1) Major bleeding is an independent predictor of in-hospital death in ACS; (2) the role of bleeding as a risk marker overcomes that as a risk factor for death. This conclusion should be seen as a hypothesis generator to be confirmed by larger-sample studies.