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

Abstract

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%; PϽ0.0001) and a 1.5-fold-higher incidence of death between 30 days and 6 months (4.6% versus 2.9%; Pϭ0.002). 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; PϽ0.0001), but the hazard was much weaker after 30 days (hazard ratio, 1.54; 95% CI, 1.01 to 2.36; Pϭ0.047). 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 trendϭ0.0009). 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.

The Challenge of Defining Bleeding Among Patients with Acute Coronary Syndromes

“…The use of combination anticoagulant therapies and invasive procedures also carries an increased risk of bleeding, which has been shown to be linked with both short-and long-term mortality in patients with ACS. 2,3 Although the recognition and evaluation of bleeding complications may seem intuitive, clinical trials and registries of patients with ACS have used different scales to classify the severity of bleeding, making cross-study comparisons difficult. Many trials also have used more than one scale, potentially confounding the assessment of the safety of various anticoagulant therapies.…”

Issues in Management of Acute Coronary Syndromes: Effects of Bleeding

“…This relationship is independent of baseline patient characteristics, comorbid conditions, and treatments and also reflects a direct correlation between the severity of bleeding and the risk of the adverse outcome. 4,5,10,11 The adjusted risk of the 30-day mortality, for example, was five times higher in ACS patients with major bleeding compared with those with no bleeding in a recent meta-analysis. 4 Major bleeding was also strongly correlated with the risk for MI or stroke within 30 days in this analysis.…”

“…4,5,10,11 The adjusted risk of the 30-day mortality, for example, was five times higher in ACS patients with major bleeding compared with those with no bleeding in a recent meta-analysis. 4 Major bleeding was also strongly correlated with the risk for MI or stroke within 30 days in this analysis. Similar relationships have been found between major bleeding and the 30-day risk of composite ischemia and stent thrombosis; 5 major bleeding is a powerful, independent predictor of 1-year mortality in patients undergoing PCI.…”

“…1 -3 However, the more widespread use of these modalities has also prompted an increase in the risk of bleeding-the presence and severity of which are major prognostic indicators in patients with ACS and in patients undergoing PCI. 4,5 To achieve optimal short-and long-term outcomes in patients with ACS, the ability to minimize the risk of ischemic events must be balanced against the increased risk of hemorrhagic events. This supplement reflects the findings of a recent roundtable discussion of experts focusing on the prevention, effects, and management of bleeding events among patients with ACS and those undergoing PCI.…”

“…Patient characteristics that have been associated with an increased risk of bleeding in ACS include advanced age, serum creatinine, and prior stroke; increased systolic blood pressure has been a significant negative predictor of major bleeding. 4 For patients undergoing PCI, in addition to advanced age and renal insufficiency, independent baseline predictors of major bleeding includes female gender, hypertension, anemia, baseline ST-segment deviation, and baseline cardiac biomarker elevation. 5 The choice and dosage of antithrombotic therapy represent an important, modifiable risk factor for bleeding in ACS and PCI patients.…”