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Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints.The MINT trial will inform RBC transfusion practice in patients with acute MI.

Background Several new trials evaluating transfusion strategies in patients with cardiovascular disease have recently been published, increasing the number of enrolled patients by over 30%. The objective was to evaluate transfusion thresholds in patients with cardiovascular disease. Methods We conducted an updated systematic review of randomized trials that compared patients assigned to maintain a lower (restrictive transfusion strategy) or higher (liberal transfusion strategy) hemoglobin concentration. We focused on new trial data in patients with cardiovascular disease. The primary outcome was 30-day mortality. Specific subgroups were patients undergoing cardiac surgery and with acute myocardial infarction. Results A total of 37 trials that enrolled 19,049 patients were appraised. In cardiac surgery, mortality at 30 days was comparable between groups (risk ratio 0.99; 95% confidence interval 0.74-1.33). In 2 small trials (n = 154) in patients with myocardial infarction, the point estimate for the mortality risk ratio was 3.88 (95% CI, 0.83-18.13) favoring the liberal strategy. Overall, from 26 trials enrolling 15,681 patients, 30-day mortality was not different between restrictive and liberal transfusion strategies (risk ratio 1.0, 95% CI, 0.86-1.16). Overall and in the cardiovascular disease subgroup, there were no significant differences observed across a range of secondary outcomes. Conclusions New trials in patients undergoing cardiac surgery establish that a restrictive transfusion strategy of 7 to 8 g/dL is safe and decreased red cell use by 24%. Further research is needed to define the optimal transfusion threshold in patients with acute myocardial infarction.

We performed a pilot trial evaluating transfusion thresholds in symptomatic cardiac disease. Pilot studies are performed to determine feasibility of a research project and often provide essential experience needed to plan a definitive study. In the MINT pilot trial, we evaluated recruitment rates, ability to implement transfusion protocol, procedures for follow-up, classification of outcomes, data collection forms, and the resources needed to carry out the study. Overall, the MINT pilot was successful, and the experience gained will result in changes in the protocol that will assure successful completion of a definitive trial. Pilot studies are not designed to answer clinical questions because the sample size required to determine the feasibility of a study is much smaller than that needed to answer a clinical question. Small trials commonly have unequal distribution of baseline characteristics even with the use of optimal randomization procedures like those used in MINT. The clinical results of small studies may not provide accurate estimate of treatment effect because of random variation. Each of these points was described in our manuscript. In response to the assertions made by Dr Sandar et al, enrollment in the trial was terminated because recruitment was slower than anticipated, the allotted recruitment period was over, and the goal of determining the feasibility of the trial had beenestablishedwith 110patients. A central telephone randomization system was used in the MINT pilot, which assures concealment of the random assignment. The differences found in baseline characteristics are common in small trials and are the result of chance. We clearly state in the methods and discussion that we defined the significant P value as b.01 for secondary outcomes and that theP valuewas .032 for death at 30 days.We reference the CRIT trial, which was performed in only 45 patients. The meta-analysis referenced by Dr Sandar is likely to be biased because all but one of the studies included in the analysis used an observational design, rather than a randomized trial design, and because of other methodological limitations of the analysis. We believe the MINT pilot raises the hypothesis that patients with acute coronary syndrome with hemoglobin level b10 g/dL might benefit from liberal transfusion to maintain the hemoglobin N10 g/dL. Approximately 25% of patients with acute coronary syndrome have hemoglobin b10 g/dL. An adequately powered clinical trial is essential to provide the evidence needed to establish the optimal transfusion threshold in patients with acute coronary syndrome.

Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients. Patients with acute coronary syndrome may benefit from higher hemoglobin levels.We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin8 g/dL. The predefined primary outcome was the composite of death, myocardial infarction, or unscheduled revascularization 30 days post randomization.Baseline characteristics were similar between groups except age (liberal, 67.3; restrictive, 74.3). The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group. The primary outcome occurred in 6 patients (10.9%) in the liberal group and 14 (25.5%) in the restrictive group (risk difference = 15.0%; 95% confidence interval of difference 0.7% to 29.3%; P = .054 and adjusted for age P = .076). Death at 30 days was less frequent in liberal group (n = 1, 1.8%) compared to restrictive group (n = 7, 13.0%; P = .032).The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy. These results support the feasibility of and the need for a definitive trial.