One-Year Major Cardiovascular Events After Restrictive Versus Liberal Blood Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Trial
2022; Lippincott Williams & Wilkins; Volume: 145; Issue: 6 Linguagem: Inglês
10.1161/circulationaha.121.057909
ISSN1524-4539
AutoresJosé Ramón González‐Juanatey, Gilles Lemesle, Étienne Puymirat, Grégory Ducrocq, Marine Cachanado, Joan Albert Arnáiz, Manuel Martínez‐Sellés, Johanne Silvain, Albert Ariza‐Solé, Émile Ferrari, Gonzalo Calvo, Nicolas Danchin, C. Avendaño, Alexandra Rousseau, Éric Vicaut, Teba González-Ferrero, Philippe Gabríel Steg, Tabassome Simon,
Tópico(s)Mechanical Circulatory Support Devices
ResumoHomeCirculationVol. 145, No. 6One-Year Major Cardiovascular Events After Restrictive Versus Liberal Blood Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Trial Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBOne-Year Major Cardiovascular Events After Restrictive Versus Liberal Blood Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Trial Jose R. Gonzalez-Juanatey, MD, Gilles Lemesle, MD, PhD, Etienne Puymirat, MD, PhD, Gregory Ducrocq, MD, PhD, Marine Cachanado, MSc, Joan Albert Arnaiz, MD, PhD, Manuel Martínez-Sellés, MD, PhD, Johanne Silvain, MD, PhD, Albert Ariza-Solé, MD, Emile Ferrari, MD, Gonzalo Calvo, MD, PhD, Nicolas Danchin, MD, Cristina Avendano-Solá, MDE, Alexandra Rousseau, PhD, Eric Vicaut, MD, PhD, Teba Gonzalez-Ferrero, MD, Philippe Gabriel Steg, MD, PhD, Tabassome Simon, MD, PhD and for the REALITY Investigators Jose R. Gonzalez-JuanateyJose R. Gonzalez-Juanatey Cardiology Department, University Hospital, Health Research Institute of Santiago de Compostela, Centro de Investigación en Red de Enfermedades Cardiovasculares, University of Santiago de Compostela, Spain (J.R.G.-J., T.G.-F.). Search for more papers by this author , Gilles LemesleGilles Lemesle Institut Cœur Poumon, Centre Hospitalier Universitaire de Lille, Faculté de Médecine de Lille, Université de Lille, French Alliance for Cardiovascular Trials, Institut Pasteur de Lille, Institut national de la santé et de la recherche médicale (INSERM) U1011 (G.L.). French Alliance for Cardiovascular Trials, Paris (G.L.). Search for more papers by this author , Etienne PuymiratEtienne Puymirat https://orcid.org/0000-0002-0533-9682 Université de Paris, AP-HP, Hôpital Européen Georges Pompidou, French Alliance for Cardiovascular Trials (E.P., N.D.). Search for more papers by this author , Gregory DucrocqGregory Ducrocq Université de Paris, AP-HP, French Alliance for Cardiovascular Trials, INSERM U1148 (G.D., P.G.S.). Search for more papers by this author , Marine CachanadoMarine Cachanado Department of Clinical Pharmacology and Clinical Research Platform of the East of Paris (Unite de Recherche Clinique de l'est parisien-Centre de Recherche Clinique-Centre de ressource biologique), AP-HP, Hôpital St Antoine, Sorbonne-Université, France (M.C., A.R.). Search for more papers by this author , Joan Albert ArnaizJoan Albert Arnaiz Clinical Trials Unit, Clinical Pharmacology Department, Hospital Clinic, Barcelona, Spain (J.A.A.). Search for more papers by this author , Manuel Martínez-SellésManuel Martínez-Sellés Sorbonne Université, ACTION Study Group, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), INSERM Unité mixte de recherche 1166, Paris, France (J.S.). Search for more papers by this author , Johanne SilvainJohanne Silvain Sorbonne Université, ACTION Study Group, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), INSERM Unité mixte de recherche 1166, Paris, France (J.S.). Search for more papers by this author , Albert Ariza-SoléAlbert Ariza-Solé University Hospital Bellvitge, Heart Disease Institute, Barcelona, Spain (A.A.-S.). Search for more papers by this author , Emile FerrariEmile Ferrari Université Côte d’Azur, and CHU de Nice, Hôpital Pasteur 1, Service de Cardiologie, French Alliance for Cardiovascular Trials (E.F.). Search for more papers by this author , Gonzalo CalvoGonzalo Calvo Àrea del Medicament, Hospital Clínic of Barcelona, University of Barcelona, Spain (G.C.). Search for more papers by this author , Nicolas DanchinNicolas Danchin https://orcid.org/0000-0001-9263-5051 Université de Paris, AP-HP, Hôpital Européen Georges Pompidou, French Alliance for Cardiovascular Trials (E.P., N.D.). Search for more papers by this author , Cristina Avendano-SoláCristina Avendano-Solá Clinical Pharmacology Service, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain (C.A.-S.). Search for more papers by this author , Alexandra RousseauAlexandra Rousseau https://orcid.org/0000-0002-9935-185X Department of Clinical Pharmacology and Clinical Research Platform of the East of Paris (Unite de Recherche Clinique de l'est parisien-Centre de Recherche Clinique-Centre de ressource biologique), AP-HP, Hôpital St Antoine, Sorbonne-Université, France (M.C., A.R.). Search for more papers by this author , Eric VicautEric Vicaut AP-HP, Department of Biostatistics, Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital, France (E.V.). Search for more papers by this author , Teba Gonzalez-FerreroTeba Gonzalez-Ferrero Cardiology Department, University Hospital, Health Research Institute of Santiago de Compostela, Centro de Investigación en Red de Enfermedades Cardiovasculares, University of Santiago de Compostela, Spain (J.R.G.-J., T.G.-F.). Search for more papers by this author , Philippe Gabriel StegPhilippe Gabriel Steg https://orcid.org/0000-0001-6896-2941 Université de Paris, AP-HP, French Alliance for Cardiovascular Trials, INSERM U1148 (G.D., P.G.S.). Imperial College, Royal Brompton Hospital, London, United Kingdom (P.G.S.). Search for more papers by this author , Tabassome SimonTabassome Simon Correspondence to: Tabassome Simon, MD, PhD, Sorbonne-Université, (APHP.SU) 27 Rue Chaligny, 75012, Paris, France. Email E-mail Address: [email protected] https://orcid.org/0000-0002-4550-0450 Department of Clinical Pharmacology-Clinical Research Platform (Unite de Recherche Clinique de l'est parisien-Centre de ressource biologique-Centre de Recherche Clinique), AP-HP.SU, Hôpital Saint Antoine, French Alliance for Cardiovascular Trials, Sorbonne-Université, Paris (T.S.). Search for more papers by this author and for the REALITY Investigators Search for more papers by this author Originally published7 Feb 2022https://doi.org/10.1161/CIRCULATIONAHA.121.057909Circulation. 2022;145:486–488Uncertainty exists on the optimal transfusion strategy in patients with anemia and acute myocardial infarction (AMI). Observational studies and 2 small randomized trials examining the effect on clinical outcomes of various transfusion strategies in AMI patients with anemia have yielded conflicting results, emphasizing the need for larger randomized clinical trials.1The REALITY trial (Restrictive and Liberal Transfusion Strategies in Patients With AMI; NCT02648113; https://clinicaltrials.gov/ct2/show/NCT00235092) is a randomized, noninferiority trial in 666 patients with AMI with anemia (hemoglobin concentration between 7 and 10 g/dL), comparing management with a restrictive transfusion strategy (transfusion triggered by hemoglobin ≤8 g/dL, with a target between 8 and 10 g/dL) or a liberal strategy (transfusion triggered by hemoglobin ≤10 g/dL, with a target >11 g/dL), used as reference.2 The primary outcome was cost–effectiveness ratio, and the main clinical end point was the composite of all-cause death, recurrent myocardial infarction, or emergency revascularization (major adverse cardiovascular event [MACE]) at 30 days. At 30 days, the main clinical outcome occurred in 11% versus 14% of patients in the restrictive and liberal arms, respectively (relative risk, 0.79 [1-sided 97.5% CI, 0−1.19]), meeting the prespecified noninferiority margin <1.25.3As prespecified, follow-up was continued to 1 year, to describe 1-year outcomes and test whether the restrictive strategy remained clinically noninferior to the liberal strategy in both intention-to-treat (n=666) and per-protocol populations (n=659; consent withdrawal in 2 and 5 patients from the restrictive and liberal strategies, respectively). The study was approved by an institutional review committee, and subjects gave written informed consent. The data that support the findings are available from the corresponding author on reasonable request.A Cox proportional-hazards model stratified on center was used to estimate the hazard ratios and 95% CIs for the effect of transfusion strategy on outcomes. Survival and MACE-free survival during 1 year are also described using Kaplan-Meier curves. In addition, relative risk was calculated for MACE.At 1 year, MACE occurred in 111 patients and 92 patients in the restrictive and liberal groups, respectively (hazard ratio, 1.16 [95% CI, 0.88−1.53]). The relative risk for MACE was 1.13, and the 1-sided 97.5% CI, 0−1.43, was no longer within the prespecified noninferiority margin of 1.25 (Figure [A]). MACE event curves appeared to cross at approximately month 5 (Figure [B]). In a post hoc exploratory analysis, the hazard ratio was 1.00 (95% CI, 0.72−1.38) <5 months and 1.71 (95% CI, 1.00−2.94) ≥5 months. All-cause death occurred in 79 patients versus 66 patients in restrictive and liberal groups, respectively.Download figureDownload PowerPointFigure. One-year major cardiovascular events.A, Relative risk of major adverse cardiovascular event (MACE; for the restrictive vs liberal groups) and 97.5% unilateral CI (intention-to-treat population). B, MACE-free survival from randomization to 1 year (intention-to-treat population). MACE is defined as the composite of all-cause death, nonfatal stroke, nonfatal recurrent myocardial infarction, or emergency revascularization prompted by ischemia. HR indicates hazard ratio.The baseline characteristics of surviving patients at day 30 did not differ between treatment groups. In a post hoc analysis of MACE between day 30 and 1 year, MACE occurred more frequently in the restrictive group (hazard ratio, 1.44 [95% CI, 1.01−2.03]).At least 1 safety event was documented in 11.8% versus 11.3% of the patients in the restrictive and the liberal groups, respectively. Safety outcomes at 1 year did not differ from those reported at day 30.3This analysis has several limitations. First, the REALITY trial was of moderate size and did not establish definitive superiority of either strategy. A larger ongoing trial with a similar design (MINT trial [Myocardial Ischemia and Transfusion]; NCT02981407) is powered to test clinical superiority of the liberal strategy using the composite outcome of all-cause death or nonfatal recurrent AMI at 6 months. Second, the trial was open-label because of the logistical challenges of blinding transfusion in the setting of AMI. However, assessment of clinical efficacy relied on objective outcomes, which were blindly adjudicated. Third, the post hoc analysis of events occurring between 30 days and 1 year must be interpreted as highly speculative and hypothesis-generating.The main finding from the 1-year analysis of the randomized REALITY trial performed in AMI patients with anemia is that, in contrast with what was observed at 30 days, a restrictive transfusion strategy versus a liberal strategy did not achieve noninferiority in terms of MACE. This may be a result of a higher rate of events (including all-cause death) in the restrictive strategy group among surviving patients after 30 days. This observation may be a chance finding, given the relatively small sample size, or may reflect potential late harm of the restrictive strategy. A late accrual of MACE in the restrictive group may reflect delayed harm related to persistent anemia, such as an increased risk of sudden death or arrhythmias in that group.4,5In conclusion, in patients with AMI and anemia, a restrictive versus liberal transfusion strategy did not achieve clinical noninferiority at 1 year. These results indicate the need for more evidence on the optimal transfusion strategy in this clinical setting.Article InformationSources of FundingThe trial was designed by the French Alliance for Cardiovascular Trials, and was funded via a grant from the Program de Recherche Médico-Economique 2015 from the French Ministry of Health and a grant from the Instituto de Salud Carlos III (Spanish Ministry of Economy and Competitiveness; grant PI15/01543). The sponsor of the trial was “Délégation à la Recherche Clinique et au Développement, Assistance Publique-Hôpitaux de Paris,” Paris, France.DisclosuresDr Gonzalez-Juanatey reports grants from Instituto de Salud Carlos III/Spanish Ministry of Health during the conduct of the study; and grants or personal fees from Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Novartis, Novo Nordisk, Pfizer, Sanofi, Ferrer International, and Tecnofarma. Dr Lemesle reports personal fees from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, MSD, Daiichi Sankyo-Lilly, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, and Servier. Dr Ducrocq reports lecture or consulting fees or travel support from Amgen, AstraZeneca, Bayer, BMS, Janssen, Sanofi, and Terumo, and participation in a Clinical Event Committee for Novo Nordisk. Dr Silvain reports consulting fees, lecture fees, or travel support from Abbott Medical France, AstraZeneca, Bayer HealthCare SAS, Boehringer-Ingelheim France, CSL Behring SA, Gilead Science, Sanofi-Aventis France, Terumo France SAS, and Zoll; and is a stockholder of 4P-Pharma. Dr Vicaut reports consulting fees from Biocompatibles for participation on a steering committee. Dr Steg reports grants from Program de Recherche Medico Economique and from Instituto de Salud Carlos III, grant No. PI15/01543; grants and personal fees from Amarin, AstraZeneca, Bayer, Sanofi, Regeneron Pharmaceuticals, and Servier; and personal fees from Amgen, Boehringer-Ingelheim, BMS, Idorsia, Myokardia, Novartis, Novo Nordisk, and Pfizer. In addition, Dr Steg has a patent as coinventor of the use of alirocumab to reduce cardiovascular risk. All rights are assigned to Sanofi. Dr Simon reports grants from Program de Recherche Medico Economique and from Instituto de Salud Carlos III, grant No. PI15/01543, Astra Zeneca, Bayer, Boehringer, Daiichi-Sankyo, Eli Lilly, GSK, Novartis, and Sanofi; and personal fees, lecture fees, or participation on a data safety monitoring board or advisory board from Ablative Solutions, AstraZeneca, Bayer, Sanofi, Servier, Novartis, and 4 Living Biotech. Dr Arnaiz reports grants and/or consulting fees or payment for expert testimony from HIPRA, Norgine, Bluebird, ViiV, Synthon, Dr Reddy’s, and Mylan. Dr Ariza-Solé reports consulting fees and/or participation on a data safety monitoring board from AstraZeneca and Bayer. Dr Calvo reports lecture or consulting fees or participation on a data safety monitoring board from Bayer, Pfizer, Novartis, Vertex, MSD, Almirall, 4 Living Biotech, Ozyzon, and Sanofi. Dr Puymirat reports grants from the French Ministry of Health and St Jude Medical, and lecture and/or consulting fees from Abbott, Amgen, AstraZeneca, BMS, Bayer, Biotronik, Boehringer-Ingelheim, Daiichi-Sankyo, Lilly, MSD, Novartis, Pfizer, Sanofi, and Servier. Dr Danchin reports lecture or consulting fees or travel support from Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Intercept, MSD, Novo Nordisk, Pfizer, Sanofi, Servier, UCB, and Vifor. The other authors report no conflicts.FootnotesThis manuscript was sent to David Morrow, Guest Editor, for review by expert referees, editorial decision, and final disposition.For Sources of Funding and Disclosures, see page 488.Correspondence to: Tabassome Simon, MD, PhD, Sorbonne-Université, (APHP.SU) 27 Rue Chaligny, 75012, Paris, France. Email tabassome.[email protected]frReferences1. Yeh RW, Wimmer NJ. Blood transfusion in myocardial infarction: opening old wounds for comparative-effectiveness research.J Am Coll Cardiol. 2014; 64:820–822. doi: 10.1016/j.jacc.2014.05.041CrossrefMedlineGoogle Scholar2. Ducrocq G, Calvo G, González-Juanatey JR, Durand-Zaleski I, Avendano-Sola C, Puymirat E, Lemesle G, Arnaiz JA, Martínez-Sellés M, Rousseau A, et al.; REALITY Investigators. Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: rationale and design of the REALITY trial.Clin Cardiol. 2021; 44:143–150. doi: 10.1002/clc.23453CrossrefMedlineGoogle Scholar3. Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, Lemesle G, Cachanado M, Durand-Zaleski I, Arnaiz JA, Martínez-Sellés M, Silvain J, Ariza-Solé A, et al.; REALITY Investigators. Effect of a restrictive vs liberal blood transfusion strategy on major cardiovascular events among patients with acute myocardial infarction and anemia: the REALITY randomized clinical trial.JAMA. 2021; 325:552–560. doi: 10.1001/jama.2021.0135CrossrefMedlineGoogle Scholar4. Goldenberg I, Barsheshet A, Laish-Farkash A, Swissa M, Schliamser JE, Michowitz Y, Glikson M, Suleiman M; Israeli Working Group on Pacing and Electrophysiology. Anemia and the risk of life-threatening ventricular tachyarrhythmias from the Israeli Implantable Cardioverter Defibrillator Registry.Am J Cardiol. 2017; 120:2187–2192. doi: 10.1016/j.amjcard.2017.08.041CrossrefMedlineGoogle Scholar5. Kim IJ, Yang PS, Kim TH, Uhm JS, Pak HN, Lee MH, Sung JH, Joung B. Relationship between anemia and the risk of sudden cardiac arrest - a nationwide cohort study in South Korea.Circ J. 2018; 82:2962–2969. doi: 10.1253/circj.CJ-18-0046CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Durand-Zaleski I, Ducrocq G, Mimouni M, Frenkiel J, Avendano-Solá C, Gonzalez-Juanatey J, Ferrari E, Lemesle G, Puymirat E, Berard L, Cachanado M, Arnaiz J, Martínez-Sellés M, Silvain J, Ariza-Solé A, Calvo G, Danchin N, Paco S, Drouet E, Abergel H, Rousseau A, Simon T and Steg P (2022) Economic evaluation of restrictive vs. liberal transfusion strategy following acute myocardial infarction (REALITY): trial-based cost–effectiveness and cost–utility analyses, European Heart Journal - Quality of Care and Clinical Outcomes, 10.1093/ehjqcco/qcac029 February 8, 2022Vol 145, Issue 6Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.057909PMID: 35130052 Originally publishedFebruary 7, 2022 Keywordsmajor cardiovascular eventsanaemiaacute myocardial infarctiontransfusionprognosisPDF download Advertisement SubjectsAcute Coronary SyndromesClinical StudiesMortality/SurvivalQuality and OutcomesTreatment
Referência(s)