Prognostic significance of bleeding location and severity among patients with acute coronary syndromes

Abstract

Objectives: This study sought to determine if there is an association between bleed location and clinical outcomes in acute coronary syndromes (ACS) patients.

Background: The prognostic significance of bleeding location among ACS patients undergoing cardiac catheterization is not well known.

Methods: We analyzed in-hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) study. Bleeding events were categorized by location as access site, systemic, surgical, or superficial, and severity was graded using the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definition. We assessed the association of each bleeding location and severity with 6-month risk of death or myocardial infarction using a multicovariate-adjusted Cox proportional hazard model.

Results: A total of 4,900 bleeding events were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679 GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were associated with an increased risk of 6-month death or myocardial infarction (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94, and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and access-site bleeds were not associated with downstream risk (adjusted HR: 1.17 [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221 GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR: 5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to 6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]).

Conclusions: Among ACS patients who develop in-hospital bleeding, systemic and surgical bleeding are associated with the highest risks of adverse outcomes regardless of bleeding severity. Although the most frequent among bleeds, GUSTO mild/moderate access-site bleeding is not associated with increased risk. These data underscore the importance of strategies to minimize overall bleeding risk beyond vascular access site management.

Keywords: ACS; CABG; CI; GP; HR; IQR; MI; PCI; TIMI; Thrombolysis In Myocardial Infarction; acute coronary syndrome; acute coronary syndromes; bleeding; confidence interval(s); coronary artery bypass graft; glycoprotein; hazard ratio(s); interquartile range; myocardial infarction; percutaneous coronary intervention.

Figure 1. Distribution of Bleeding Events in SYNERGY by GUSTO Severity and Location

Figure displays counts of bleeding events by location and severity. Patients may have >1 bleeding event. Only bleeding events occurring prior to the death or myocardial infarction outcome are included. CABG = coronary artery bypass graft; GI = gastrointestinal; GUSTO = Global Use of Strategies To Open Occluded Coronary Arteries; SYNERGY = Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors.

Figure 2. Risk of Bleeding in Each Location Stratified by CRUSADE Bleeding Prediction Score

Kaplan-Meier estimates of bleeding risk at 14 days (90th percentile of length of stay) in each bleeding location, stratified by CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) score category.

Figure 3. Hazard Ratio for the Risk of 6-Month Death or MI Associated with Bleeding Severity and Location

Covariates for 6-month death/myocardial infarction (MI) were adapted from a previously developed and validated risk model for 6-month death or MI in the SYNERGY dataset and included age, sex, race, height, geographic location, history of diabetes, tobacco use, prior MI, creatinine, heart rate on admission, Killip class, randomization to enoxaparin (vs. unfractionated heparin), and the composite of age ≥60 years, ST-segment depression of admission electrocardiogram, and positive cardiac biomarkers. In this bleed-level analysis, each hazard ratio (HR) quantifies the increased risk associated with a particular bleed location and severity compared with an absence of that type of bleed. CI = confidence interval(s); other abbreviations as in Figure 1.