Original Research
1 October 2024

Effect of Four Hemoglobin Transfusion Threshold Strategies in Patients With Acute Myocardial Infarction and Anemia: A Target Trial Emulation Using MINT Trial Data

Publication: Annals of Internal Medicine
Volume 177, Number 11
Visual Abstract. Effect of Four Hemoglobin Transfusion Threshold Strategies in Patients With Acute Myocardial Infarction and Anemia
The optimal hemoglobin threshold to guide red blood cell transfusion for patients with acute myocardial infarction and anemia is uncertain. This prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial, which randomly assigned patients to a liberal transfusion threshold versus a more restrictive threshold, used target trial emulation methods to compare 4 transfusion strategies to maintain patients’ hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL.

Abstract

Background:

The optimal hemoglobin threshold to guide red blood cell (RBC) transfusion for patients with acute myocardial infarction (MI) and anemia is uncertain.

Objective:

To estimate the efficacy of 4 individual hemoglobin thresholds (<10 g/dL [<100 g/L], <9 g/dL [<90 g/L], <8 g/dL [<80 g/L], and <7 g/dL [<70 g/L]) to guide transfusion in patients with acute MI and anemia.

Design:

Prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial using target trial emulation methods. (ClinicalTrials.gov: NCT02981407)

Setting:

144 clinical sites in 6 countries.

Participants:

3492 MINT trial participants with acute MI and a hemoglobin level below 10 g/dL.

Intervention:

Four transfusion strategies to maintain patients’ hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Protocol exceptions were permitted for specified adverse clinical events.

Measurements:

Data from the MINT trial were leveraged to emulate 4 transfusion strategies and estimate per protocol effects on the composite outcome of 30-day death or recurrent MI (death/MI) and 30-day death using inverse probability weighting.

Results:

The 30-day risk for death/MI was 14.8% (95% CI, 11.8% to 18.4%) for a <10-g/dL strategy, 15.1% (CI, 11.7% to 18.2%) for a <9-g/dL strategy, 15.9% (CI, 12.4% to 19.0%) for a <8-g/dL strategy, and 18.3% (CI, 14.6% to 22.0%) for a <7-g/dL strategy. Absolute risk differences and risk ratios relative to the <10-g/dL strategy for 30-day death/MI increased as thresholds decreased, although 95% CIs were wide. Findings were similar and imprecise for 30-day death.

Limitation:

Unmeasured confounding may have persisted despite adjustment.

Conclusion:

The 30-day risks for death/MI and death among patients with acute MI and anemia seem to increase progressively with lower hemoglobin concentration thresholds for transfusion. However, the imprecision around estimates from this target trial analysis precludes definitive conclusions about individual hemoglobin thresholds.

Primary Funding Source:

National Heart, Lung, and Blood Institute.

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Supplemental Material

Supplemental Material

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 177Number 11November 2024
Pages: 1489 - 1498

History

Published online: 1 October 2024
Published in issue: November 2024

Keywords

Authors

Affiliations

Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.T.P., S.A.S.)
Division of General Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey (J.L.C.)
Sonja A. Swanson, ScD
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (G.T.P., S.A.S.)
John H. Alexander, MD, MHS https://orcid.org/0000-0002-1444-2462
Duke Clinical Research Institute, Duke University, Durham, North Carolina (J.H.A., R.D.L.)
Paul C. Hébert, MD, MHSc
Bruyere Research Institute, University of Ottawa, Ottawa, Ontario, Canada (P.C.H.)
Shaun G. Goodman, MD, MSc https://orcid.org/0000-0001-8068-2440
St. Michael’s Hospital, Unity Health Toronto, and Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada, and Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada (S.G.G.)
Philippe Gabriel Steg, MD
Université Paris-Cité and French Alliance for Cardiovascular Trials (FACT), Paris, France (P.G.S.)
Department of Epidemiology and Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (M.B., M.M.B.)
Jordan B. Strom, MD, MSc https://orcid.org/0000-0002-6592-6141
Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (J.B.S.)
Dean A. Fergusson, PhD, MHA https://orcid.org/0000-0002-3389-2485
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (D.A.F.)
Tabassome Simon, MD, PhD https://orcid.org/0000-0002-4550-0450
French Alliance for Cardiovascular Trials (FACT); Sorbonne Université; and Assistance Publique – Hôpitaux de Paris (AP-HP), Service de Pharmacologie, Plateforme de Recherche, Clinique de l’Est Parisien, Hospital Saint Antoine, Paris, France (T.S.)
Green Lane Clinical Coordinating Centre, Auckland, New Zealand (H.D.W.)
Howard A. Cooper, MD
Department of Cardiology, Westchester Medical Center, Valhalla, New York (H.A.C.)
Division of Cardiology, Warren Alpert Medical School, Brown University, Providence, Rhode Island (J.D.A.)
Sunil V. Rao, MD
Department of Medicine, NYU Langone Health System, New York, New York (S.V.R.)
Division of Cardiology, St. Louis University School of Medicine, St. Louis, Missouri (B.R.C.)
Christopher B. Fordyce, MD, MHS, MSc https://orcid.org/0000-0002-4050-1518
Division of Cardiology, Vancouver General Hospital, and Centre for Cardiovascular Innovation, University of British Columbia, Vancouver, British Columbia, Canada (C.B.F.)
Renato D. Lopes, MD, PhD https://orcid.org/0000-0003-2999-4961
Duke Clinical Research Institute, Duke University, Durham, North Carolina (J.H.A., R.D.L.)
Benoit Daneault, MD
Université de Sherbrooke, Sherbrooke, Quebec, Canada (B.D.).
Department of Epidemiology and Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (M.B., M.M.B.)
Acknowledgment: This research was supported in part by the University of Pittsburgh Center for Research Computing, RRID:SCR_022735, through the resources provided. Specifically, this work used the H2P cluster, which is supported by National Science Foundation award number OAC-2117681. The authors thank Dr. Leonardo Bernasconi for his consultation in utilizing these resources.
Grant Support: The MINT trial was funded by the National Heart, Lung, and Blood Institute (U01 HL133817, U01HL132853) and the Canadian Blood Services and Canadian Institutes of Health Research Institute of Circulatory and Respiratory Health (grant 342193) and was supported in part by the RHU iVASC grant #ANR-16-RHUS-00010 from the French National Research Agency as part of the Investment for the Future Program.
Reproducible Research Statement: Study protocol: The MINT trial protocol is available in reference 1. Statistical code: Available from Dr. Brooks (e-mail, [email protected]). Data set: The data will be publicly available at the National Heart, Lung, and Blood Institute's BioLINCC beginning in December 2025.
Corresponding Author: Maria M. Brooks, PhD, Department of Epidemiology, University of Pittsburgh, 4420 Bayard Street, Suite 600, Pittsburgh, PA 15260; e-mail, [email protected].
Author Contributions: Conception and design: G.T. Portela, S.A. Swanson, M.M. Brooks.
Analysis and interpretation of the data: G.T. Portela, J.L. Carson, S.A. Swanson, J.H. Alexander, P.C. Hébert, S.G. Goodman, P.G. Steg, M. Bertolet, J.B. Strom, D.A. Fergusson, T. Simon, H.D. White, H.A. Cooper, J.D. Abbott, R.D. Lopes, B. Daneault, M.M. Brooks.
Drafting of the article: G.T. Portela, J.L. Carson, P.C. Hébert.
Critical revision for important intellectual content: G.T. Portela, J.L. Carson, S.A. Swanson, J.H. Alexander, P.C. Hébert, S.G. Goodman, P.G. Steg, M. Bertolet, J.B. Strom, D.A. Fergusson, T. Simon, H.D. White, H.A. Cooper, J.D. Abbott, S.V. Rao, B.R. Chaitman, C.B. Fordyce, R.D. Lopes, B. Daneault, M.M. Brooks.
Final approval of the article: G.T. Portela, J.L. Carson, S.A. Swanson, J.H. Alexander, P.C. Hébert, S.G. Goodman, P.G. Steg, M. Bertolet, J.B. Strom, D.A. Fergusson, T. Simon, H.D. White, H.A. Cooper, J.D. Abbott, S.V. Rao, B.R. Chaitman, C.B. Fordyce, R.D. Lopes, B. Daneault, M.M. Brooks.
Provision of study materials or patients: J.L. Carson, T. Simon, M.M. Brooks.
Statistical expertise: G.T. Portela, S.A. Swanson, M. Bertolet, M.M. Brooks.
Obtaining of funding: J.L. Carson, P.C. Hébert, S.G. Goodman, P.G. Steg, M.M. Brooks.
Administrative, technical, or logistic support: J.L. Carson, B.R. Chaitman, M.M. Brooks.
Collection and assembly of data: G.T. Portela, J.L. Carson, P.C. Hébert, S.G. Goodman, P.G. Steg, M. Bertolet, J.B. Strom, T. Simon, H.D. White, H.A. Cooper, J.D. Abbott, S.V. Rao, B.R. Chaitman, C.B. Fordyce, R.D. Lopes, B. Daneault, M.M. Brooks.
This article was published at Annals.org on 1 October 2024.
*
A full list of the MINT Investigators is provided in the Supplement.

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Gerard T. Portela, Jeffrey L. Carson, Sonja A. Swanson, et al. Effect of Four Hemoglobin Transfusion Threshold Strategies in Patients With Acute Myocardial Infarction and Anemia: A Target Trial Emulation Using MINT Trial Data. Ann Intern Med.2024;177:1489-1498. [Epub 1 October 2024]. doi:10.7326/M24-0571

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