1. Publication
- Title: Liberal or Restrictive Postoperative Transfusion in Patients at High Cardiac Risk: The TOP Randomized Clinical Trial
- Acronym: TOP
- Year & Journal: JAMA, epublished November 8, 2025 (print: 2025;334(24):2197-2207)
- Citation: Kougias P, Sharath SE, Zhan M, et al; TOP Trial Investigators. JAMA. 2025;334(24):2197-2207. doi:10.1001/jama.2025.20841
2. Context & Rationale
Background: Restrictive transfusion (Hb<7 g/dL) is standard in stable hospitalized patients, but its safety specifically in high-cardiac-risk postoperative patients was unclear, since postoperative anemia may worsen oxygen delivery and precipitate ischemic events in this vulnerable population.
Research Question/Hypothesis: In veterans at high cardiac risk with postoperative anemia after major vascular/general surgery, does a liberal (Hb<10) vs restrictive (Hb<7) transfusion strategy reduce 90-day death, MI, revascularization, AKI, or ischemic stroke?
3. Design & Methods
- Study Type: RCT (VA cooperative study)
- Setting & Centers: US VA hospitals; Feb 2018–Mar 2023
- Population: 1428 veterans (mean age 70y, 98% male) undergoing major vascular/general surgery, postop Hb<10
- Intervention: Liberal transfusion (trigger Hb<10)
- Comparator: Restrictive transfusion (trigger Hb<7; 2 units if <5.5, 1 unit if 5.5-7)
- Statistical Power & Follow-Up: Primary: 90-day composite of death, MI, revascularization, AKI, ischemic stroke.
4. Key Results
1424 patients with data.
Outcome | Liberal | Restrictive | Effect Size | 95% CI | Notes |
90-day composite (primary) | 9.1% | 10.1% | RR 0.90 | 0.65–1.24 | No significant difference |
Cardiac complications other than MI | Fewer | More | Not reported | — | Restrictive group had more non-MI cardiac complications |
Subgroup analyses (age, cardiac risk) | No significant difference | — | — | — | Consistent null across prespecified subgroups |
5. Internal Validity Assessment
Adequately powered (1428-patient) VA cooperative trial with clear transfusion protocols. Overall: Strong — clean null primary result with a genuinely informative secondary signal (fewer non-MI cardiac complications with liberal strategy).
6. External Validity Assessment
VA population (98% male, mean age 70) undergoing major vascular/general surgery — well-representative of high-cardiac-risk surgical populations, though the veteran-predominant, male-predominant cohort may limit generalizability to broader surgical populations.
7. Strengths & Limitations
Strengths: Adequately powered, pragmatic, clinically relevant threshold comparison; directly addresses guideline uncertainty for this specific high-risk population.
Limitations: Predominantly male veteran population; no significant difference in the primary composite despite the cardiac-complication signal.
8. Interpretation & Practice Impact
Supports continued restrictive transfusion as the default in most stable high-cardiac-risk postoperative patients, but the secondary signal (more non-MI cardiac complications with restrictive strategy) suggests individualizing toward a more liberal approach in patients with ischemic heart disease, symptomatic heart failure, arrhythmias, or recent coronary events — rigid Hb thresholds may not suffice for this complex population.
9. Controversies & Subsequent Evidence
Accompanying JAMA editorial ("Postoperative Transfusion in Patients at High Cardiac Risk: Evidence, Uncertainty, and Nuance") explicitly calls for individualized, rather than purely threshold-based, transfusion decisions in this population.
10. Summary & Executive Takeaway
Summary: TOP randomized 1428 high-cardiac-risk veterans with postoperative anemia to liberal (Hb<10) or restrictive (Hb<7) transfusion. The 90-day composite outcome was not significantly different (9.1% vs 10.1%, RR 0.90), but restrictive transfusion was associated with more non-MI cardiac complications.
Overall Takeaway: Restrictive transfusion remains reasonable as a default even in high-cardiac-risk postoperative patients, but the cardiac-complication signal supports individualized decision-making — more liberal transfusion may be warranted in patients with active ischemic heart disease or heart failure, rather than applying a single rigid threshold to all high-risk patients.
11. Bibliography
- Jacobs JW, Bloch EM. Postoperative Transfusion in Patients at High Cardiac Risk: Evidence, Uncertainty, and Nuance [editorial]. JAMA. 2025.
- Carson JL, et al. Restrictive vs liberal transfusion thresholds (systematic review context).