Transfusion Thresholds for Acute Coronary Syndromes—Insights From the TRICS-III Randomized Controlled Trial, Systematic Review, and Meta-Analysis

Abstract

Both anemia and red blood cell transfusion are associated with morbidity and mortality in patients hospitalized for acute coronary syndromes (ACSs); these exposures are tightly linked, and their attributable risks are difficult to isolate. To reduce unnecessary blood exposure, transfusion should only be administered if/when its net benefits outweigh the risks associated with anemia. Hemoglobin thresholds are currently used for evaluating the severity of anemia and for guiding transfusion therapy; however, there is controversy surrounding the optimal hemoglobin threshold for transfusion in this patient population.1 Randomized controlled trials (RCT) comparing hemoglobin-guided restrictive versus liberal transfusion strategies are difficult to interpret,2 and there is a paucity of available data on long-term outcomes. We therefore performed a subset analysis of patients with acute myocardial infarction (AMI) in the TRICS-III (Transfusion Thresholds in Cardiac Surgery) RCT to add evidence addressing this important clinical question and further interpret the results using a systematic-review, meta-analysis, and trial-sequential analysis. The previously described3 multinational TRICS-III trial (NCT02042898) randomly assigned patients with a moderate-to-high risk of death undergoing cardiac surgery on cardiopulmonary bypass to a restrictive transfusion strategy (transfuse at a hemoglobin level <7.5 g/dL) or liberal strategy (operating room and intensive care unit: transfuse at a hemoglobin level <9.5 g/ dL; ward: <8.5 g/dL). Appropriate ethical board review and approval were obtained from each participating site, and informed consent was obtained from all participants. Patients with AMI were those with a recent myocardial infarction (MI) (<90 days of surgery) undergoing coronary artery bypass graft surgery and ≥1 of the following enrichment criteria: unstable angina, critical preoperative state, use of preoperative intra-aortic balloon pump, and/or undergoing emergency surgery. The primary outcome was a per-protocol analysis of major adverse cardiac events (MACE) defined as allcause death, MI, and revascularization at 6 months. We next performed a systematic search of the MEDLINE and EMBASE databases from inception to April 18, 2022, to identify RCTs evaluating restrictive versus liberal transfusion in patients hospitalized for ACSs. The primary outcome was MACE, defined as all-cause death, MI, and revascularization (when available), at the longest available timepoint.