Key Points:
- In patients at high cardiac risk undergoing major vascular or general surgery and developing postoperative anemia, a liberal transfusion strategy (Hb < 10) did not significantly reduce 90-day mortality or major ischemic events compared with a restrictive strategy (Hb < 7)
- The primary outcome (composite of all-cause mortality, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke at 90 days) occurred in 9.1% in the liberal group vs. 10.1% in the restrictive group (RR 0.90, 95% CI 0.65-1.24)
- A secondary endpoint, cardiac complications excluding MI (arrhythmias, heart failure, or non-fatal cardiac arrest), was significantly lower in the liberal group (5.9%) versus the restrictive group (9.9%) (RR 0.59, 99% CI 0.36-0.98)
Postoperative anemia is common after major surgeries and carries increased risk of morbidity and mortality, especially among patients with high underlying cardiac risk. Prior guideline recommendations generally support a restrictive transfusion strategy (e.g., Hb < 7) for stable hospitalized patients, but it remained uncertain whether that paradigm applies in patients undergoing major operations who are at elevated risk of cardiac events. The TOP Trial (“Transfusion Trigger after Operations in High Cardiac Risk Patients” (ClinicalTrials.gov identifier NCT03229941) presented at American Heart Association Scientific Sessions 2025 with simultaneous publication in JAMA was designed to fill this evidence gap.
This was a parallel, single-blind, randomized superiority trial conducted across 16 U.S. Veterans Affairs medical centers, enrolling 1,428 veterans (mean age 70, 98% male) from February 2018 to March 2023. Patients who underwent major vascular or general surgery and developed a postoperative hemoglobin below 10 were randomized: 714 to the liberal strategy (transfuse when Hb < 10) and 714 to the restrictive strategy (transfuse when Hb < 7). The primary endpoint was a 90-day composite of death, myocardial infarction, coronary revascularization, acute kidney failure or ischemic stroke.
In the primary analysis (n = 1,424), the primary outcome occurred in 9.1% of patients in the liberal-transfusion arm vs. 10.1% in the restrictive arm (RR 0.90, 95% CI 0.65-1.24), a non-significant difference. The mean hemoglobin difference between strategies was about 2.0 g/dL by day 5 post-randomization. For the key secondary endpoint of non-MI cardiac complications, the restrictive group suffered more events (9.9% vs. 5.9%; RR 0.59; 99% CI 0.36-0.98), suggesting a possible signal favoring the liberal strategy in that domain. Major bleeding, transfusion-related complications, and other safety endpoints did not differ meaningfully between groups.
The TOP trial demonstrated that, in a high cardiac risk surgical population, adopting a liberal transfusion threshold (Hb < 10) compared with a restrictive threshold (Hb < 7) did not lead to a statistically significant reduction in the primary composite outcome of death or major ischemic events at 90 days. That suggests that simply raising the hemoglobin target post-operatively may not yield broad benefit in this setting. At the same time, the observed reduction in non-MI cardiac complications in the liberal group opens the possibility that some sub-domains of cardiac risk may be modifiable by transfusion strategy, though this conclusion needs cautious interpretation and further investigation.
Importantly, the investigators emphasize that transfusion decisions in high-cardiac-risk postoperative patients should not rely solely on a fixed hemoglobin trigger, but rather integrate broader clinical variables (e.g., patient symptoms, cardiac biomarkers, perfusion status) and individualized context. As lead author Panos Kougias, MD noted in one interview: “We were surprised that the restrictive transfusion strategy – giving less blood by only transfusing once patients’ hemoglobin levels were below 7 g/dL – did not clearly show non-inferiority in this high-risk surgical cohort, and our results reinforce the need for more nuanced, individualized transfusion decisions.”
In summary, the TOP trial provides important, practice-influencing data in a previously under-studied patient population. While a restrictive transfusion strategy remains safe broadly, caution is warranted when applying the lowest thresholds in patients with elevated cardiac risk following major surgery. Its findings support further work to refine transfusion thresholds using patient-specific risk profiles rather than universal hemoglobin triggers.
