Restrictive versus Liberal Transfusion Strategies in Acute Myocardial Infarction and Anemia: A Meta-Analysis and Trial Sequential Analysis

Background: The optimal transfusion strategy in acute myocardial infarction (AMI)-associated anemia remains uncertain. Objectives: To compare all-cause mortality between liberal versus restrictive transfusion strategies in patients with AMIassociated anemia, using a meta-analytic approach. Methods: Pubmed, Embase, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) comparing liberal and restrictive transfusion strategies in AMI-associated anemia. Random-effects meta-analysis and trial sequential analysis (TSA) were conducted to compare blood use, efficacy, and safety endpoints. The p-values were 2-sided with an alpha of 0.05. Results: In a pooled analysis involving 4,217 participants from three RCTs followed-up for 30 days, no statistically significant differences emerged between restrictive and liberal strategies in all-cause mortality (RR 1.03; 95% CI 0.67-1.57; p=0.90) and other efficacy endpoints (recurrent AMI, unscheduled revascularization, acute heart failure, stroke, and acute kidney injury), as well as in safety endpoints including allergic reactions, infection, and acute lung injury. TSA did not reach futility boundaries. In patients assigned to restrictive strategy, substantial differences in transfusion use were observed across RCTs, correlating with mortality rates, and likely accounting for between-study heterogeneity in treatment effects. Conclusions: In patients with AMI-associated anemia, there is no clear superiority between liberal and restrictive transfusion strategies in all-cause mortality or other major outcomes in 30 days. However, the heterogeneity observed in blood use between the restrictive groups likely explains variable findings across RCTs.