Clinical Question: In patients with high cardiac risk who develop postoperative anemia after major vascular or general surgery, does a liberal transfusion strategy reduce 90-day death or major ischemic events compared to a restrictive strategy?
Background: Postoperative anemia is common after major surgery and is associated with increased morbidity and mortality, particularly in patients with known cardiac disease. Current guidelines recommend a restrictive transfusion threshold for most hospitalized patients, but the safety of this approach in high cardiac risk patients is an ongoing debate. Prior trials have suggested potential harm from restrictive transfusion in patients with ischemic heart disease due to already limited oxygen delivery, creating clinical ambiguity for this vulnerable population.
Study Design: Parallel, single-blind, randomized, clinical superiority trial
Setting: 16 Veterans Affairs medical centers in the U.S.
Synopsis: 1,428 veterans with a history of ischemic cardiac, peripheral artery, or cerebrovascular disease were enrolled from February 2018 to March 2023 and were randomized after developing postoperative hemoglobin under 10 g/dL following major surgery. Patients received either a liberal transfusion strategy (hemoglobin less than 10 g/dL) or a restrictive strategy (hemoglobin less than 7 g/dL), achieving a mean hemoglobin separation of 2.0 g/dL by day five. The primary composite outcome, comprised of 90-day all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or stroke, was similar between groups (9.1% for the liberal strategy versus 10.1% for the restrictive; relative risk [RR], 0.90; 95% CI, 0.65 to 1.24). One-year all-cause mortality was similar between groups. However, a prespecified secondary outcome of non-myocardial-infarction cardiac complications—including new arrhythmias and heart failure—was significantly lower in the liberal group (5.9% versus 9.9%; RR, 0.59; 99% CI, 0.36 to 0.98). When myocardial infarction was included in the post hoc analysis, the difference was no longer statistically significant (8.2% versus 12.5%; RR, 0.66; 99% CI, 0.43 to 1.01). The trial was underpowered due to lower-than-anticipated event rates and early funding termination.
Bottom Line: A liberal transfusion strategy did not significantly reduce 90-day death or major ischemic cardiac outcomes compared to a restrictive strategy in postoperative, high-risk cardiac patients, supporting the safety of current restrictive transfusion guidelines in this population. The reduction in non-myocardial-infarction cardiac complications with liberal transfusion is an intriguing secondary finding that warrants further study.
Citation: Kougias P, et al. Liberal or restrictive postoperative transfusion in patients at high cardiac risk: the TOP randomized clinical trial. JAMA. 2025;334(24):2197–2207. doi:10.1001/jama.2025.20841.
Dr. Lu
Dr. Lu is a hospital medicine fellow in the division of hospital medicine at UC San Diego in San Diego.