The results of a blood transfusion strategy study, the Myocardial Ischemia and Transfusion (MINT) trial, have been published in the New England Journal of Medicine. This phase III, open label, randomized interventional trial sought to assess, “whether the risk of death or myocardial infarction through 30 days differed between a restrictive transfusion strategy (hemoglobin threshold, 7 to 8 g per deciliter) and a liberal transfusion strategy (hemoglobin threshold, <10 g per deciliter) among patients with an acute myocardial infarction and anemia.”
The merits of a liberal versus restrictive blood transfusion strategy continues to be discussed within the blood community. International blood transfusion guidelines in the form of blood transfusion recommendations were published earlier this year. The investigators explained that, “[i]ndications for red-cell transfusion remain controversial in patients [with an acute myocardial infarction and anemia]” due to a lack of evidence. They described the benefits and risks of blood transfusions, “[f]rom a mechanistic perspective, blood transfusion may decrease is-chemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death. Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”
The MINT trial exploration of a liberal versus restrictive blood transfusion strategy in patients with acute myocardial infarction and anemia took place at 144 sites in the U.S. Canada, France, Brazil, New Zealand, and Australia. It included adults 18 years of age or older “with-segment elevation or non–ST-segment elevation myocardial infarction [and] anemia (hemoglobin level, <10 g per deciliter within 24 hours before randomization)…Patients were ineligible for enrollment if they had uncontrolled bleeding, were receiving palliative treatment, were scheduled for cardiac surgery during the current admission, or had declined to receive blood transfusion…Patients were randomly assigned in a 1:1 ratio to a restrictive or liberal [blood] transfusion strategy.”
For the restrictive-blood transfusion strategy group, the authors explained that, “transfusion was permitted but not required when the hemoglobin level was less than 8 g per deciliter and was strongly recommended when the level was less than 7 g per deciliter or when anginal symptoms were not controlled with medications. In the liberal-blood transfusion strategy group, one unit of packed red cells was administered after randomization and red cells were transfused to maintain the hemoglobin level at or above 10 g per deciliter until the time of hospital discharge or 30 days.”
The investigators stated that 3,504 patients were enrolled in the MINT trial between April 2017 and April 2023 and included in the statistical analyses. “The mean hemoglobin level was lower in the restrictive-blood transfusion strategy group than in the liberal-blood transfusion strategy group by 1.3 g per deciliter (95 percent confidence interval [CI], 1.2 to 1.4) on day 1 and lower by 1.6 g per deciliter (95 percent CI, 1.5 to 1.7) on day 3. The total number of units of red cells that were transfused in the liberal-strategy group was 3.5 times the number that were transfused in the restrictive-strategy group (4,325 units vs. 1,237 units). The mean (±SD) number of red-cell units that were transfused in the liberal-strategy group was 2.5±2.3, as compared with 0.7±1.6 in the restrictive-strategy group. The median duration of hospitalization from randomization until discharge, withdrawal, or death was five days (interquartile range, 2 to 10) in the two groups.”
The blood transfusion strategy trial found that, “[m]yocardial infarction or death from any cause at 30 days (the primary outcome) occurred in 295 of 1,749 patients (16.9 percent) in the restrictive-blood transfusion strategy group and in 255 of 1,755 patients (14.5 percent) in the liberal-strategy group…At 30 days, death had occurred in 173 of 1,749 patients (9.9 percent) in the restrictive-blood transfusion strategy group and in 146 of 1,755 patients (8.3 percent) in the liberal-strategy group (risk ratio, 1.19; 95 percent CI, 0.96 to 1.47), and myocardial infarction had occurred in 8.5 percent and 7.2 percent of the patients, respectively (risk ratio, 1.19; 95 percent CI, 0.94 to 1.49). Death, myocardial infarction, ischemia-driven unscheduled coronary revascularization, or readmission to the hospital for an ischemic cardiac condition within 30 days occurred in 19.6 percent of the patients in the restrictive-blood transfusion strategy group and in 17.4 percent of those in the liberal-strategy group (risk ratio, 1.13; 95 percent CI, 0.98 to 1.29).” The authors also explained that, “[c]ardiac death was more common in the restrictive-blood transfusion strategy group than in the liberal-strategy group (5.5 percent and 3.2 percent, respectively; risk ratio, 1.74; 95 percent CI, 1.26 to 2.40); the risk of other clinical-outcome events did not differ significantly between the two groups. The risk of heart failure at 30 days was similar in the restrictive-blood transfusion strategy group and the liberal-blood transfusion strategy group (5.8 percent and 6.3 percent, respectively; risk ratio, 0.92; 95 percent CI, 0.71 to 1.20), although there were fewer transfusion-associated cardiac overload (TACO) events in the restrictive-strategy group than in the liberal-strategy group (0.5 percent and 1.3 percent, respectively; risk ratio, 0.35; 95 percent CI, 0.16 to 0.78).”
The investigators concluded that, “[o]ur results show that in patients with acute myocardial infarction and anemia, a liberal blood transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. Trial end points suggest some benefit of a liberal blood transfusion strategy over a restrictive blood transfusion strategy, but additional studies would be needed to confirm that conclusion.” They noted that, “[t]he findings in our trial contrast with the results from previous transfusion trials conducted across a wide range of patient populations and treatments (including cardiac surgery).” Limitations of the MINT trial included, “[a]s in all transfusion-threshold trials, the assigned intervention was not masked from health professionals caring for the patients. This factor may have influenced the use of revascularization or other interventions or the classification of cause of death. Death from cardiac causes was a prespecified outcome, but it was not designated as a primary, secondary, or tertiary outcome and was not adjudicated, and fewer than half the deaths were classified as cardiac…[T]rial analyses were not adjusted for multiplicity, so caution must be used in interpreting the results beyond the primary outcome.”
Citation: Carson, J.L., Brooks, M.M., Hébert, P.C., et al. “Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia.” NEJM. 2023.