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

Abstract

Importance: The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear.

Objective: To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy.

Design, setting, and participants: Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019.

Interventions: Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy.

Main outcomes and measures: The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome.

Results: Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups.

Conclusions and relevance: Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm.

Trial registration: ClinicalTrials.gov Identifier: NCT02648113.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Danchin reported receiving personal fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Intercept, MSD, Novo Nordisk, Pfizer, Sanofi, Servier, UCB, and Vifor outside the submitted work. Dr Ducrocq reported receiving personal fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Sanofi, and Terumo outside the submitted work. Dr Durand-Zaleski reported receiving grants from the Ministry of Health during the conduct of the study and personal fees from Vifor outside the submitted work and being the chair of the scientific committee of the French Blood Establishment. Dr Lemesle reported receiving personal fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, MSD, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, and Servier outside the submitted work. Dr Puymirat reported receiving fees for lectures and/or consulting from Amgen, AstraZeneca, Bristol Myers Squibb, Bayer, Biotronick, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Pfizer, The Medicines Company, Sanofi, St Jude Medical, and Servier. Dr Silvain reported receiving grants and personal fees from AstraZeneca; personal fees from Bayer HealthCare, Boehringer Ingelheim France, BPI France, CSL Behring, Gilead Science, Sanofi-Aventis France, and Zoll; and nonfinancial support from Abbott Medical France and Terumo France and being a stockholder in Pharmaseeds outside the submitted work. Dr Simon reported receiving grants from the Programme de Recherche Medico Economique and the Instituto de Salud Carlos III (PI15/01543) for Spanish centers in the trial during the conduct of the study and personal fees from AstraZeneca, Novartis, Sanofi, Astellas, and MSD and grants from AstraZeneca, Bayer, Boehringer, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Novartis, and Sanofi outside the submitted work. Dr Steg reported receiving grants from the French Ministry of Health and the Spanish Ministry of Industry during the conduct of the study and grants from Amarin, Bayer, Sanofi (Odyssey Outcomes co-chair), and Servier (CLARIFY registry chair) and personal fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Idorsia, Novartis, Novo Nordisk, Pfizer, Sanofi, Myokardia, Phase Bio, and Janssen outside the submitted work. Dr Vicaut reported receiving personal fees from Abbott for consulting outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Flow of Patients in a Study of the Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia

aThe initial protocol specified a threshold of 7 g/dL. This was changed to 8 g/dL to maximize investigator adherence to the protocol before inclusion of the first patient. Enrollment took place at any time during hospitalization. No screening log was maintained.

Figure 2.. Rate of Major Adverse Cardiovascular Events in a Study of the Effect of a Restrictive vs Liberal Blood Transfusion Strategy Among Patients With Acute Myocardial Infarction and Anemia

Results shown are of analyses including the as-randomized population. All patients were followed up to the first event or 30 days. Major adverse cardiovascular events are a composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia.