Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Nov 8:e2520841.
doi: 10.1001/jama.2025.20841. Online ahead of print.

Liberal or Restrictive Postoperative Transfusion in Patients at High Cardiac Risk: The TOP Randomized Clinical Trial

Panos Kougias  1 , Sherene E Sharath  1 , Min Zhan  2 , Jeffrey L Carson  3 , L Erin Norman  2 , Zhibao Mi  2 , Rupsi Pal  2 , Hasan Dosluoglu  4 , J Gregory Modrall  5 , George A Sarosi Jr  6 , Peter Nelson  7 , Shipra Arya  8 , Alexandra Scrymgeour  9 , Jade Ollison  1 , Lawrence A Calais  10 , Vijay Nambi  11 , L Parker Gregg  12 , Shuaib M Abdullah  13 , Shirling Tsai  5 , Natasha Becker  1 , Justin C Choi  1 , Louisa Chiu  12 , Salvatore Scali  6 , Neal R Barshes  14 , Samir Awad  14 , Mohammed Moursi  15 , Matthew C Koopmann  16 , Mitchell Sally  17 , Daniel Ihnat  18 , Archana Ramaswamy  18 , Warren Gasper  19 , Edith Tzeng  20 , Mark A Wilson  20 , Gale Tang  21 , Grant Huang  2 , Kousick Biswas  2 ; TOP Trial Investigators
Collaborators, Affiliations

Liberal or Restrictive Postoperative Transfusion in Patients at High Cardiac Risk: The TOP Randomized Clinical Trial

Panos Kougias et al. JAMA. .

Abstract

Importance: Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear.

Objective: To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia.

Design, setting, and participants: This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac risk undergoing major vascular or general surgery operations. Participants were enrolled from February 2018 to March 2023 across 16 Veterans Affairs Medical Centers in the US.

Interventions: Seven hundred fourteen participants with postoperative hemoglobin less than 10 g/dL were randomized to a liberal strategy (transfusion trigger at hemoglobin level <10 g/dL) and 714 to a restrictive strategy (transfusion trigger at hemoglobin <7 g/dL).

Main outcomes and measures: The primary end point was a composite of all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke within 90 days after randomization. Secondary end points included a composite of cardiac complications other than myocardial infarction (arrhythmias, heart failure, and nonfatal cardiac arrest).

Results: Of the 1424 analyzed veterans (mean age, 69.9 [SD, 7.9] years; 1393 male [97.8%]; 268 Black [18.8%]; 48 Hispanic [4.1%]; 1071 White [75.2%]), 1297 (91.1%) underwent vascular surgical procedures. The mean hemoglobin difference between transfusion strategies was 2.0 g/dL on day 5 after randomization. The primary outcome rate in the liberal group was 9.1% (61 of 670) compared with 10.1% (71 of 700) in the restrictive group (relative risk, 0.90; 95% CI, 0.65-1.24). The secondary end point of cardiac complications without myocardial infarction, which was 1 of 5 secondary end points, occurred in 5.9% (38 of 647) of patients in the liberal group and 9.9% (67 of 678) of patients in the restrictive group (relative risk, 0.59; 99% CI, 0.36-0.98).

Conclusions and relevance: After major vascular or general surgery operations among patients at high risk of a cardiac event, a liberal transfusion strategy did not reduce 90-day death or major ischemic outcome rates compared with a restrictive strategy.

Trial registration: ClinicalTrials.gov Identifier: NCT03229941.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zhan reported receiving grants from Department of Veterans Affairs and being employed at the VA Caregiver Support Program during the conduct of the study. Dr Carson reported serving as the chair of a data and safety monitoring board for Cerus and receiving lecture fees from Bristol Myers Squibb outside the submitted work. Dr Mi reported being employed at the VA Caregiver Support Program during the conduct of the study. Dr Sarosi Jr reported receiving grants from the Department of Veterans Affairs during the conduct of the study. Dr Arya reported receiving grants from the VA Health Systems Research, American Heart Association, and National Heart, Lung, and Blood Institute and consulting fees from Gore Medical and Novartis outside the submitted work. Dr Nambi reported receiving grants from the VA cooperative study during the conduct of the study; having sold stock in Roche laboratories; having stock options with Insera; and serving as a site coinvestigator for Ionis Pharmaceuticals and a site champion for the Valor Quality Improvement Project. Dr Koopmann reported receiving grants from Endologix, Terumo Aortic, Gore, and Nectero Medical for clinical trials outside the submitted work. Dr Wilson reported serving as a full-time government employee of Department of Veterans Affairs. Dr Tang reported receiving grants from the VA Office of Research and Development Study that were funded by VA Cooperative Studies during the conduct of the study. No other disclosures were reported.

Comment in

References

    1. Kougias P, Sharath S, Barshes NR, Chen M, Mills JL Sr. Effect of postoperative anemia and baseline cardiac risk on serious adverse outcomes after major vascular interventions. J Vasc Surg. 2017;66(6):1836-1843. doi: 10.1016/j.jvs.2017.05.113 - DOI - PubMed
    1. Kougias P, Sharath S, Mi Z, Biswas K, Mills JL. Effect of postoperative permissive anemia and cardiovascular risk status on outcomes after major general and vascular surgery operative interventions. Ann Surg. 2019;270(4):602-611. doi: 10.1097/SLA.0000000000003525 - DOI - PubMed
    1. Carson JL, Terrin ML, Noveck H, et al. ; FOCUS Investigators . Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365(26):2453-2462. doi: 10.1056/NEJMoa1012452 - DOI - PMC - PubMed
    1. Hajjar LA, Vincent JL, Galas FR, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559-1567. doi: 10.1001/jama.2010.1446 - DOI - PubMed
    1. Hébert PC, Wells G, Blajchman MA, et al. ; Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group . A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care: N Engl J Med. 1999;340(6):409-417. doi: 10.1056/NEJM199902113400601 - DOI - PubMed

Associated data