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Transfusion Thresholds for Acute Coronary Syndromes—Insights From the TRICS‐III Randomized Controlled Trial, Systematic Review, and Meta‐Analysis

2022; Wiley; Volume: 12; Issue: 1 Linguagem: Inglês

10.1161/jaha.122.028497

2047-9980

Nikhil Mistry, Gregory M. T. Hare, Nadine Shehata, Emilie P. Belley‐Côté, Fábio de Vasconcelos Papa, Robert S. Kramer, Tarit Saha, Duminda N. Wijeysundera, Dennis T. Ko, Subodh Verma, C. David Mazer,

Erythropoietin and Anemia Treatment

HomeJournal of the American Heart AssociationVol. 12, No. 1Transfusion Thresholds for Acute Coronary Syndromes—Insights From the TRICS‐III Randomized Controlled Trial, Systematic Review, and Meta‐Analysis Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessLetterPDF/EPUBTransfusion Thresholds for Acute Coronary Syndromes—Insights From the TRICS‐III Randomized Controlled Trial, Systematic Review, and Meta‐Analysis Nikhil Mistry, Gregory M. T. Hare, Nadine Shehata, Emilie Belley‐Cote, Fabio Papa, Robert S. Kramer, Tarit Saha, Duminda N. Wijeysundera, Dennis Ko, Subodh Verma and C. David Mazer Nikhil MistryNikhil Mistry , Department of Anesthesia, , St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Institute of Medical Sciences, , University of Toronto, , Ontario, , Gregory M. T. HareGregory M. T. Hare , Department of Anesthesia, , St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Department of Anesthesiology and Pain Medicine, , University of Toronto, , Ontario, , Canada, , Department of Physiology, , University of Toronto, , Ontario, , Canada, , Li Ka Shing Knowledge Institute of St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Nadine ShehataNadine Shehata , Division of Hematology, , Sinai Health System, , Toronto, , Ontario, , Canada, , Department of Medicine, , University of Toronto, , Ontario, , Canada, , Emilie Belley‐CoteEmilie Belley‐Cote , Population Health Research Institute, , McMaster University, Hamilton Health Sciences, , Hamilton, , Ontario, , Fabio PapaFabio Papa , Department of Anesthesia, , St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Department of Anesthesiology and Pain Medicine, , University of Toronto, , Ontario, , Canada, , Robert S. KramerRobert S. Kramer , Maine Medical Center Cardiovascular Institute, , Portland, , ME, , Tarit SahaTarit Saha , Department of Anesthesiology and Perioperative Medicine, , Kingston General Hospital, , Kingston, , Ontario, , Canada, , Duminda N. WijeysunderaDuminda N. Wijeysundera https://orcid.org/0000-0002-5897-8605 , Department of Anesthesia, , St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Department of Anesthesiology and Pain Medicine, , University of Toronto, , Ontario, , Canada, , Li Ka Shing Knowledge Institute of St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Dennis KoDennis Ko https://orcid.org/0000-0001-6840-8051 , Schulich Heart Centre Sunnybrook, , Health Sciences Centre, , Toronto, , Ontario, , Canada, , Subodh VermaSubodh Verma , Institute of Medical Sciences, , University of Toronto, , Ontario, , Li Ka Shing Knowledge Institute of St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Division of Cardiac Surgery, , St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Department of Surgery, , University of Toronto, , Ontario, , Canada, , Department of Pharmacology and Toxicology, , University of Toronto, , Ontario, , Canada, and C. David MazerC. David Mazer * Correspondence to: C. David Mazer, MD, Department of Anesthesia, Unity Health Toronto, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. Email: E-mail Address: [email protected] https://orcid.org/0000-0003-2566-4308 , Department of Anesthesia, , St. Michael's Hospital, , Toronto, , Ontario, , Canada, , Institute of Medical Sciences, , University of Toronto, , Ontario, , Department of Anesthesiology and Pain Medicine, , University of Toronto, , Ontario, , Canada, , Department of Physiology, , University of Toronto, , Ontario, , Canada, , Li Ka Shing Knowledge Institute of St. Michael's Hospital, , Toronto, , Ontario, , Canada, Originally published24 Dec 2022https://doi.org/10.1161/JAHA.122.028497Journal of the American Heart Association. 2023;12:e028497Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 24, 2022: Ahead of Print Both anemia and red blood cell transfusion are associated with morbidity and mortality in patients hospitalized for acute coronary syndromes (ACSs); these exposures are tightly linked, and their attributable risks are difficult to isolate. To reduce unnecessary blood exposure, transfusion should only be administered if/when its net benefits outweigh the risks associated with anemia. Hemoglobin thresholds are currently used for evaluating the severity of anemia and for guiding transfusion therapy; however, there is controversy surrounding the optimal hemoglobin threshold for transfusion in this patient population.1 Randomized controlled trials (RCT) comparing hemoglobin‐guided restrictive versus liberal transfusion strategies are difficult to interpret,2 and there is a paucity of available data on long‐term outcomes. We therefore performed a subset analysis of patients with acute myocardial infarction (AMI) in the TRICS‐III (Transfusion Thresholds in Cardiac Surgery) RCT to add evidence addressing this important clinical question and further interpret the results using a systematic‐review, meta‐analysis, and trial‐sequential analysis.The previously described3 multinational TRICS‐III trial (NCT02042898) randomly assigned patients with a moderate‐to‐high risk of death undergoing cardiac surgery on cardiopulmonary bypass to a restrictive transfusion strategy (transfuse at a hemoglobin level <7.5 g/dL) or liberal strategy (operating room and intensive care unit: transfuse at a hemoglobin level <9.5 g/dL; ward: <8.5 g/dL). Appropriate ethical board review and approval were obtained from each participating site, and informed consent was obtained from all participants. Patients with AMI were those with a recent myocardial infarction (MI) ( 1% reduction in absolute risk) and do not exclude important harm (do not exclude ≥6% increases in absolute risk). At 40% of the critical information size, the trial‐sequential analysis for MACE did not cross the boundary for superiority or futility, suggesting more evidence is needed to consider this association as conclusive.Prior meta‐analyses demonstrating no clinical benefit of a restrictive or liberal transfusion strategy in ACS have been limited by a lack of availability of data and ability to evaluate only short‐term outcomes. We provide new, high‐quality, randomized data on long‐term outcomes and synthesize the results across RCTs with low clinical, methodological, and statistical heterogeneity. Our findings suggest that liberal transfusion strategies may decrease the risk for long‐term MACE and MI. This effect was similar across trials evaluating patients primarily receiving nonsurgical and surgical management of ACS.It is possible that differences in preexisting anemia or transfusion protocol suspensions may have led to bias in the effect estimates. Emerging evidence suggests that restrictive transfusion strategies are no longer cost‐effective after 1 year6; therefore, adoption of liberal strategies may improve patient outcomes without increasing cost burden to the health care system. This unrealized benefit may be considerably large, as 5 of 6 respondents from a recent poll by the American College of Cardiology reported using a restrictive transfusion strategy in their current clinical practice for this patient population.7 Long‐term data from the ongoing MI and ischemia RCT (NCT02981407) will provide evidence for establishing the conclusiveness of our findings.In summary, a liberal transfusion strategy versus restrictive strategy may improve long‐term cardiovascular outcomes in patients hospitalized for ACSs. Further investigation is needed to elucidate the mechanisms contributing to this effect and confirm these findings.Sources of FundingFunding provided by the Canadian Institutes of Health Research (232416 and 301852), the Kenneth J. Fyke Award from the Canadian Blood Services–Health Canada, the National Health and Medical Research Council of Australia (1085942), the Health Research Council of New Zealand (16/353), and the University of Toronto Department of Anesthesiology and Pain Medicine (Merit Awards). The funders of this study did not contribute in any way to the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.DisclosuresN. Mistry, Dr Hare, Dr Shehata, Dr Belley‐Cote, Dr Papa, Dr Kramer, Dr Saha, Dr Verma, and Dr Mazer are coauthors of the TRICS‐III (Transfusion Thresholds in Cardiac Surgery) trial. Dr Ko is supported by the Jack Tu Chair in Cardiovascular Outcomes Research, Sunnybrook Hospital and University of Toronto. Dr Verma holds a Tier 1 Canada Research Chair in Cardiovascular Surgery and reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, EOCI Pharmacomm Ltd, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not‐for‐profit physician organization. Dr Mazer reports advisory board honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, BioAge, and PhaseBio. Dr Belley‐Cote reports receiving research grants from Bristol Myers Squibb‐Pfizer, Bayer, and Roche Diagnostics.AcknowledgmentsWe thank the TRICS‐III (Transfusion Thresholds in Cardiac Surgery) investigators, participants, and other health care clinicians at participating institutions for their contributions to the study and for allowing the ability to collect these data.Footnotes* Correspondence to: C. David Mazer, MD, Department of Anesthesia, Unity Health Toronto, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8. Email: david.[email protected].toFor Sources of Funding and Disclosures, see page 3 and 4.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02042898.References1 Mueller MM, Van Remoortel H, Meybohm P, Aranko K, Aubron C, Burger R, Carson JL, Cichutek K, De Buck E, Devine D, et al. Patient blood management: recommendations from the 2018 Frankfurt consensus conference. JAMA. 2019; 321:983–997. doi: 10.1001/jama.2019.0554CrossrefMedlineGoogle Scholar2 Gonzalez‐Juanatey JR, Lemesle G, Puymirat E, Ducrocq G, Cachanado M, Arnaiz JA, Martínez‐Sellés M, Silvain J, Ariza‐Solé A, Ferrari E, et al. One‐year major cardiovascular events after restrictive versus liberal blood transfusion strategy in patients with acute myocardial infarction and anemia: the REALITY randomized trial. Circulation. 2022; 145:486–488. doi: 10.1161/circulationaha.121.057909LinkGoogle Scholar3 Mazer CD, Whitlock RP, Fergusson DA, Belley‐Cote E, Connolly K, Khanykin B, Gregory AJ, de Médicis É, Carrier FM, McGuinness S, et al. Six‐month outcomes after restrictive or liberal transfusion for cardiac surgery. N Engl J Med. 2018; 379:1224–1233. doi: 10.1056/NEJMoa1808561CrossrefMedlineGoogle Scholar4 Cooper HA, Rao SV, Greenberg MD, Rumsey MP, McKenzie M, Alcorn KW, Panza JA. Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study). Am J Cardiol. 2011; 108(8):1108–1111. doi: 10.1016/j.amjcard.2011.06.014CrossrefMedlineGoogle Scholar5 Carson JL, Brooks MM, Abbott JD, Chaitman B, Kelsey SF, Triulzi DJ, Srinivas V, Menegus MA, Marroquin OC, Rao SV, et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J. 2013; 165(6):964–971.e1. doi: 10.1016/j.ahj.2013.03.001CrossrefMedlineGoogle Scholar6 Durand‐Zaleski I, Ducrocq G, Mimouni M, Frenkiel J, Avendano‐Solá C, Gonzalez‐Juanatey JR, Ferrari E, Lemesle G, Puymirat E, Berard L, et al. Economic evaluation of restrictive vs. liberal transfusion strategy following acute myocardial infarction (REALITY): trial‐based cost effectiveness and cost utility analyses. Eur Heart J Qual Care Clin Outcomes. 2022. doi: 10.1093/ehjqcco/qcac029CrossrefGoogle Scholar7 Kontos MC. American College of Cardiology. Poll Results: Hemoglobin Threshold for Transfusion in AMI. Available at: https://www.acc.org/latest‐in‐cardiology/articles/2021/07/19/13/42/poll‐results‐hemoglobin‐threshold‐for‐transfusion‐in‐ami. 2021. Accessed June 29, 2022.Google Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails January 3, 2023Vol 12, Issue 1 Article InformationMetrics Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.122.028497PMID: 36565203 Manuscript receivedOctober 14, 2022Manuscript acceptedNovember 9, 2022Originally publishedDecember 24, 2022 Keywordsacute myocardial infarctionacute coronary syndromestransfusionanemiaPDF download SubjectsAcute Coronary SyndromesMeta AnalysisMyocardial Infarction