BACKGROUND:Data on the differential impact of interventions on subsequent myocardial infarction (MI) type are limited. OBJECTIVES:This post-hoc analysis was done to evaluate the 30-day rate of subsequent MI by type (ie, type 1 and 2) among patients enrolled in the MINT (Myocardial Ischemia and Transfusion; NCT02981407) trial. METHODS:Subdistribution HRs and cumulative incidences of subsequent MI types were computed using Fine-Gray subdistribution models that accounted for the competing risk of death and other MI types, if applicable. Effect modification of treatment strategy by index MI type was tested using log-binomial regression models. RESULTS:Among 3,504 MINT trial patients, 275 (7.8%) had a 30-day subsequent MI, of which 118 (43%) were type 2 MI, 79 (28%) were uncertain MI type, 40 (15%) were type 4 MI, and 38 (14%) were type 1 MI. The rate of subsequent type 2 MI in patients randomized to the restrictive vs liberal transfusion was 3.5% (n = 61) vs 3.2% (n = 57) (HR: 1.07; 95% CI: 0.74-1.53) as compared with a subsequent type 1 MI rate of 1.3% (n = 23) vs 0.9% (n = 15) (HR: 1.53; 95% CI: 0.80-2.94). CONCLUSIONS:Among patients with MI and anemia, subsequent MI occurred within 30 days in 7.8% of patients, with type 2 MI occurring 3 times more often than type 1 MI. A differential effect of the restrictive vs liberal transfusion strategy on the type of subsequent MI (eg, type 1 vs type 2) was not observed.

BACKGROUND:The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes. The Myocardial Ischemia and Transfusion trial (MINT) randomized patients with AMI and anemia to restrictive or liberal transfusion thresholds, but sex-stratified outcomes remain undefined. The objective was to evaluate whether the clinical effect of restrictive versus liberal red blood cell transfusion strategies differs by sex in patients hospitalized with AMI and anemia. METHODS:In this prespecified secondary analysis of the MINT trial, we examined outcomes by sex and transfusion strategy. The primary outcome was 30-day composite death or MI. Secondary outcomes included heart failure, stroke, cardiac death, and 180-day mortality. Adjusted relative risks (RRs) and hazard ratios (HRs) were estimated accounting for sex differences at baseline. Interactions between sex and transfusion effects were assessed. RESULTS:There were 3504 study participants, of whom 1593 (45.4%) were women. Women received fewer transfusions on average. Primary outcome occurred in 15.7% of women and 15.7% of men and occurred in 16.5% of women and 17.1% of men in the restrictive arm, versus 14.9% and 14.2% in the liberal arm, respectively. Women had a lower mortality between 30 and 180 days (11.0% versus 13.5%; P=0.04). There were no statistically significant interactions between sex and transfusion strategy for the primary outcome (interaction P=0.60). For 30-day cardiac death, a higher RR in men was observed in the restrictive transfusion arm (RR, 2.34; 95% CI, 1.48-3.70; interaction P=0.05). CONCLUSIONS:For MINT patients with anemia and AMI, women comprised nearly half of the study population, and randomization to a restrictive or liberal transfusion strategy resulted in comparable outcomes in women and men. These findings support sex-neutral transfusion thresholds. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.

For patients with anemia and myocardial infarction (MI), the randomized, 3,504-patient MINT trial found that a liberal transfusion threshold (10 g/dL) may be preferable to a restrictive threshold (8 g/dL) in terms of death or MI. The relative effects of liberal versus restrictive transfusion in younger and older patients are unknown. The present prespecified MINT substudy found no significant interaction between age and transfusion strategy for death or MI, heart failure, revascularization procedures, cardiac death, pulmonary embolism or deep vein thrombosis, bacteremia or pneumonia, and death at 30 and 180 days. A liberal transfusion approach appears to be safe and may be the preferred transfusion strategy in anemic patients with MI, regardless of age. MINT Trial, ClinicalTrials.gov Number NCT02981407, https://www.minttrial.org/.

Importance:The decision to transfuse a patient with myocardial infarction (MI) and anemia at a higher vs lower hemoglobin threshold must consider the potential benefit of reduced risk of 30-day death or MI and the potential risk of heart failure. Objectives:To estimate bayesian posterior risk differences and posterior probabilities that a liberal vs restrictive transfusion strategy is associated with reduced risk of 30-day death or MI and whether the probabilities exceed predefined thresholds. Design, Setting, and Participants:The Myocardial Ischemia and Transfusion (MINT) trial recruited adults from April 26, 2017, to April 14, 2023, who were hospitalized with MI and anemia at 144 sites in 6 countries. Statistical analysis was performed from July 31, 2024, to February 18, 2026. Intervention:The MINT trial randomized participants to a restrictive (transfuse if hemoglobin is <7 to 8 g/dL) or liberal (maintain hemoglobin at >10 g/dL) transfusion strategy. Main Outcomes and Measures:Bayesian posterior risk differences were estimated for 30-day death or MI and for heart failure using 3 prior beliefs regarding the treatment strategies: noninformative, liberal strategy superiority, or restrictive strategy superiority. Results:The mean (SD) age of the 3504 participants was 72.1 (11.6) years and 1911 (54.5%) were men. Compared with the restrictive strategy, the risk of 30-day death or MI with the liberal strategy was 1.4% (95% credible interval, -0.8% to 3.5%) to 2.4% (95% credible interval, 0.3%-4.6%) lower, depending on prior beliefs. The probability that the liberal strategy was associated with a lower risk of 30-day death or MI ranged from 89.1% to 98.8%, and the probability that a liberal strategy was associated with at least 1 less death or MI per 100 treated was between 62.7% and 90.4%. Conversely, the risk of heart failure with the liberal strategy was 0.2% (95% credible interval, -1.6% to 1.2%) to 0.6% (95% credible interval, -2.0% to 0.8%) higher compared with the restrictive strategy, depending on prior beliefs. The probability that the liberal strategy was associated with a higher risk of heart failure ranged from 60.6% to 80.0%, and the probability that a liberal strategy was associated with at least 1 more heart failure event per 100 treated was between 13.3% and 29.3%. Conclusions and Relevance:This post hoc analysis of a randomized clinical trial of patients with MI and anemia suggests that a liberal transfusion strategy was associated with a lower risk of 30-day death or MI, outweighing the increased risk of heart failure. Consistent with guideline recommendations and according to patients' values and clinician risk assessment, a liberal transfusion strategy may be reasonable. Trial Registration:ClinicalTrials.gov Identifier: NCT02981407.

Importance The decision to transfuse a patient with myocardial infarction (MI) and anemia at a higher vs lower hemoglobin threshold must consider the potential benefit of reduced risk of 30-day death or MI and the potential risk of heart failure. Objectives To estimate bayesian posterior risk differences and posterior probabilities that a liberal vs restrictive transfusion strategy is associated with reduced risk of 30-day death or MI and whether the probabilities exceed predefined thresholds. Design, Setting, and Participants The Myocardial Ischemia and Transfusion (MINT) trial recruited adults from April 26, 2017, to April 14, 2023, who were hospitalized with MI and anemia at 144 sites in 6 countries. Statistical analysis was performed from July 31, 2024, to February 18, 2026. Intervention The MINT trial randomized participants to a restrictive (transfuse if hemoglobin is <7 to 8 g/dL) or liberal (maintain hemoglobin at >10 g/dL) transfusion strategy. Main Outcomes and Measures Bayesian posterior risk differences were estimated for 30-day death or MI and for heart failure using 3 prior beliefs regarding the treatment strategies: noninformative, liberal strategy superiority, or restrictive strategy superiority. Results The mean (SD) age of the 3504 participants was 72.1 (11.6) years and 1911 (54.5%) were men. Compared with the restrictive strategy, the risk of 30-day death or MI with the liberal strategy was 1.4% (95% credible interval, −0.8% to 3.5%) to 2.4% (95% credible interval, 0.3%-4.6%) lower, depending on prior beliefs. The probability that the liberal strategy was associated with a lower risk of 30-day death or MI ranged from 89.1% to 98.8%, and the probability that a liberal strategy was associated with at least 1 less death or MI per 100 treated was between 62.7% and 90.4%. Conversely, the risk of heart failure with the liberal strategy was 0.2% (95% credible interval, −1.6% to 1.2%) to 0.6% (95% credible interval, −2.0% to 0.8%) higher compared with the restrictive strategy, depending on prior beliefs. The probability that the liberal strategy was associated with a higher risk of heart failure ranged from 60.6% to 80.0%, and the probability that a liberal strategy was associated with at least 1 more heart failure event per 100 treated was between 13.3% and 29.3%. Conclusions and Relevance This post hoc analysis of a randomized clinical trial of patients with MI and anemia suggests that a liberal transfusion strategy was associated with a lower risk of 30-day death or MI, outweighing the increased risk of heart failure. Consistent with guideline recommendations and according to patients’ values and clinician risk assessment, a liberal transfusion strategy may be reasonable. Trial Registration ClinicalTrials.gov Identifier: NCT02981407

We conducted a series of analyses to estimate the per-protocol effect of restrictive versus liberal transfusion strategies on 30-day death and death or recurrent myocardial infarction (MI) among patients from the Myocardial Ischemia and Transfusion (MINT) trial. Multiple analytic approaches were used to estimate the per-protocol effect, including analyses based on different definitions of adherence (site-reported, time-based, transfusion delay) and an instrumental variable analysis. Analyses based on adherence definitions found a restrictive strategy was associated with a substantially greater risk of 30-day death or recurrent MI, while the instrumental variable analysis estimated a moderate treatment effect similar to the original ITT result.

OBJECTIVES:Anemia is common in critically ill patients. In prior trials, a restrictive transfusion strategy was at least as effective as, and possibly superior to, a liberal strategy in critically ill adult patients. However, the Transfusion Requirements in Critical Care (TRICC) trial suggested that a restrictive strategy might be harmful in critically ill patients with ischemic heart disease. Our objective was to compare outcomes for restrictive and liberal transfusion strategies in critically ill and noncritically ill patients with acute myocardial infarction (AMI) and anemia. DESIGN:Subgroup analysis of a parallel, two-arm randomized, controlled trial. SETTING:One hundred forty-four sites in the United States, Canada, France, Brazil, New Zealand, and Australia. PATIENTS:Adult patients with AMI and anemia enrolled in the Myocardial Ischemia and Transfusion (MINT) trial. Patients being treated in an ICU at randomization were considered critically ill. INTERVENTIONS:Patients were randomly assigned to a restrictive (transfuse when hemoglobin < 7-8 g/dL) or liberal (transfuse when hemoglobin < 10 g/dL) transfusion strategy. MEASUREMENTS AND MAIN RESULTS:We determined the effect of transfusion strategy on death and the composite of death/myocardial infarction (MI) at 30 days among critically ill and noncritically ill patients. Of 3504 patients enrolled in MINT, 1679 (47.9%) were critically ill. At 30 days, death (11.9% vs. 6.5%) and death/MI (18.9% vs. 12.7%) occurred more frequently in critically ill patients compared with noncritically ill patients. A restrictive, compared with a liberal, transfusion strategy resulted in a nonsignificant increase in the risk of death by 9% (risk ratio [RR], 1.09; 95% CI, 0.77-1.54) and death/MI by 9% (RR, 1.09; 95% CI, 0.85-1.38) in noncritically ill patients and a nonsignificant increase in the risk of death by 24% (RR, 1.24; 95% CI, 0.95-1.61; interaction p = 0.55) and death/MI by 21% (RR, 1.21; 95% CI, 0.99-1.47; interaction p = 0.52) in critically ill patients. CONCLUSIONS:There is no evidence that the overall MINT trial results, which generally favor a liberal transfusion strategy in AMI patients, apply differently to noncritically ill and critically ill patients.

BACKGROUND:Most clinical practice guidelines recommend restrictive red cell transfusion practices, with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). OBJECTIVES:To examine the evidence for the effect of transfusion thresholds on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. SEARCH STRATEGY:Trials were identified by: computer searches of the Cochrane Central Register of Controlled Trials (the Cochrane Library Issue 3, 2009), OVID MEDLINE (1966 to August 2009), Current Contents (1993 to November 2004), and the Web of Science (2004 to August 2009). References in identified trials and review articles were checked and experts contacted to identify any additional trials. SELECTION CRITERIA:Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which an RBC transfusion was to be administered. DATA COLLECTION AND ANALYSIS:Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials, using a random effects model. The risk of bias was assessed. MAIN RESULTS:Seventeen trials involving a total of 3746 patients were identified. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 37% (RR=0.63; 95% CI 0.54 to 0.74). This equates to an average absolute risk reduction (ARR) of 33% (95% CI 21% to 45%). The volume of RBCs transfused was reduced on average by 0.75 units (95% CI 0.20 to 1.30 units). However, heterogeneity between trials was statistically significant (P<0.001; I²≥74%) for these outcomes. Restrictive transfusion strategies did not appear to impact on the rate of adverse events compared to liberal transfusion strategies (i.e. mortality, cardiac events, myocardial infarction, stroke, pneumonia and thromboembolism). Restrictive transfusion strategies were associated with a statistically significant reduction in the rates of infection (RR=0.76; 95% CI 0.60 to 0.97). The use of restrictive transfusion strategies did not reduce hospital or intensive care length of stay. AUTHORS' CONCLUSIONS:The existing evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood, the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

Importance:Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear. Objective:To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia. Design, Setting, and Participants:This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac risk undergoing major vascular or general surgery operations. Participants were enrolled from February 2018 to March 2023 across 16 Veterans Affairs Medical Centers in the US. Interventions:Seven hundred fourteen participants with postoperative hemoglobin less than 10 g/dL were randomized to a liberal strategy (transfusion trigger at hemoglobin level <10 g/dL) and 714 to a restrictive strategy (transfusion trigger at hemoglobin <7 g/dL). Main Outcomes and Measures:The primary end point was a composite of all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke within 90 days after randomization. Secondary end points included a composite of cardiac complications other than myocardial infarction (arrhythmias, heart failure, and nonfatal cardiac arrest). Results:Of the 1424 analyzed veterans (mean age, 69.9 [SD, 7.9] years; 1393 male [97.8%]; 268 Black [18.8%]; 48 Hispanic [4.1%]; 1071 White [75.2%]), 1297 (91.1%) underwent vascular surgical procedures. The mean hemoglobin difference between transfusion strategies was 2.0 g/dL on day 5 after randomization. The primary outcome rate in the liberal group was 9.1% (61 of 670) compared with 10.1% (71 of 700) in the restrictive group (relative risk, 0.90; 95% CI, 0.65-1.24). The secondary end point of cardiac complications without myocardial infarction, which was 1 of 5 secondary end points, occurred in 5.9% (38 of 647) of patients in the liberal group and 9.9% (67 of 678) of patients in the restrictive group (relative risk, 0.59; 99% CI, 0.36-0.98). Conclusions and relevance:After major vascular or general surgery operations among patients at high risk of a cardiac event, a liberal transfusion strategy did not reduce 90-day death or major ischemic outcome rates compared with a restrictive strategy. Trial Registration:ClinicalTrials.gov Identifier: NCT03229941.

BackgroundClinical guidelines have concluded that there are insufficient data to provide recommendations for the hemoglobin threshold for the use of red cell transfusion in patients with acute myocardial infarction (MI) and anemia. After the recent publication of the Myocardial Infarction and Transfusion (MINT) trial, we performed an individual patient-level data meta-analysis to evaluate the effect of restrictive versus liberal blood transfusion strategies.MethodsWe conducted searches in major databases. Eligible trials randomly assigned patients with MI and anemia to either a restrictive (i.e., transfusion threshold of 7-8 g/dl) or liberal (i.e., transfusion threshold of 10 g/dl) red cell transfusion strategy. We used individual patient data from each trial. The primary outcome was a composite of 30-day mortality or MI.ResultsWe included 4311 patients from four trials. The primary outcome occurred in 334 patients (15.4%) in the restrictive strategy and 296 patients (13.8%) in the liberal strategy (relative risk [RR] 1.13, 95% confidence interval [CI], 0.97 to 1.30). Death at 30 days occurred in 9.3% of patients in the restrictive strategy and in 8.1% of patients in the liberal strategy (RR 1.15, 95% CI, 0.95 to 1.39). Cardiac death at 30 days occurred in 5.5% of patients in the restrictive strategy and in 3.7% of patients in the liberal strategy (RR 1.47, 95% CI, 1.11 to 1.94). Heart failure (RR 0.89, 95% CI, 0.70 to 1.13) was similar in the transfusion strategies. All-cause mortality at 6 months occurred in 20.5% of patients in the restrictive strategy compared with 19.1% of patients in the liberal strategy (hazard ratio 1.08, 95% CI, 1.05 to 1.11).ConclusionsPooling individual patient data from four trials did not find a definitive difference in our primary composite outcome of MI or death at 30 days. At 6 months, a restrictive transfusion strategy was associated with increased all-cause mortality. (Partially funded by a grant from the U.S. National Heart, Lung, and Blood Institute [R01HL171977].) Among adults with myocardial infarction, targeting a higher transfusion threshold (i.e., transfusion threshold of 10 g/dl) might lead to improved all-cause mortality based on an individual patient meta-analysis of four randomized trials.

Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear. To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia. This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac risk undergoing major vascular or general surgery operations. Participants were enrolled from February 2018 to March 2023 across 16 Veterans Affairs Medical Centers in the US. Seven hundred fourteen participants with postoperative hemoglobin less than 10 g/dL were randomized to a liberal strategy (transfusion trigger at hemoglobin level <10 g/dL) and 714 to a restrictive strategy (transfusion trigger at hemoglobin <7 g/dL). The primary end point was a composite of all-cause death, myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke within 90 days after randomization. Secondary end points included a composite of cardiac complications other than myocardial infarction (arrhythmias, heart failure, and nonfatal cardiac arrest). Of the 1424 analyzed veterans (mean age, 69.9 [SD, 7.9] years; 1393 male [97.8%]; 268 Black [18.8%]; 48 Hispanic [4.1%]; 1071 White [75.2%]), 1297 (91.1%) underwent vascular surgical procedures. The mean hemoglobin difference between transfusion strategies was 2.0 g/dL on day 5 after randomization. The primary outcome rate in the liberal group was 9.1% (61 of 670) compared with 10.1% (71 of 700) in the restrictive group (relative risk, 0.90; 95% CI, 0.65-1.24). The secondary end point of cardiac complications without myocardial infarction, which was 1 of 5 secondary end points, occurred in 5.9% (38 of 647) of patients in the liberal group and 9.9% (67 of 678) of patients in the restrictive group (relative risk, 0.59; 99% CI, 0.36-0.98). After major vascular or general surgery operations among patients at high risk of a cardiac event, a liberal transfusion strategy did not reduce 90-day death or major ischemic outcome rates compared with a restrictive strategy. ClinicalTrials.gov Identifier: NCT03229941

Description: Optimal transfusion strategies for patients with acute myocardial infarction (AMI) are uncertain. The aim of this guideline is to provide recommendations for red blood cell transfusion in patients with AMI. Methods: These guidelines are based on evidence from randomized controlled trials of patients presenting with AMI and assigned to 2 different transfusion strategies (restrictive or liberal) based on hemoglobin concentrations or hematocrit levels before receipt of a transfusion. A meta-analysis of eligible trials was performed using Cochrane methods. The international panel followed GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods to summarize evidence and formulate recommendations. This guideline's primary perspective is that of the patient, including medical, financial, and psychological effects, with secondary consideration of health care system issues, particularly conservation of the limited and costly blood supply. Recommendation: For hospitalized patients with AMI, the panel suggests a liberal red cell transfusion strategy when the hemoglobin concentration is less than 10 g/dL (conditional recommendation, low-certainty evidence). A restrictive strategy of 7 to 8 g/dL may result in increased mortality in patients with AMI. The direction of the recommendation for the liberal strategy was based on the great importance of mortality for patients. The conditional recommendation was based on the low certainty of evidence and the competing consideration of blood supply conservation. Clinicians should adopt mitigation strategies to reduce potential adverse events associated with a liberal transfusion strategy, and all transfusion decisions should incorporate the clinical context rather than solely the hemoglobin concentration.

A recent Perspective in Blood suggested that previous evidence from over a decade ago established that a liberal rather than a restrictive blood transfusion strategy results in better outcomes in patients with anemia and either acute myocardial infarction or stable cardiovascular disease. Their premise was that physiological evidence, and a different interpretation of the Transfusion Requirements in Critical Care (TRICC) trial should have been sufficient to establish clinical practice. They also suggest that a more personalized approach to the administration of transfusions would have been made possible by including a usual-care arm in all transfusion trials. In this counterpoint Perspective, we describe how and why 2 discrete and common blood transfusion thresholds were selected in the TRICC, FOCUS, REALITY, and MINT trials. We explain why a usual-care arm would have been uninformative. We also propose that we still do not have evidence to provide firm transfusion recommendations in several specific subpopulations of patients, including those with stable atherosclerotic coronary artery disease. Finally, we provide our perspective on the state of existing evidence and on the clinical recommendations that should be adopted in practice.

BACKGROUND:Blood transfusion may precipitate adverse outcomes, including heart failure (HF), among patients with acute myocardial infarction (MI). This study characterizes the effects of a restrictive or liberal transfusion strategy on outcomes in patients with MI and anemia with and without baseline HF. METHODS:In the MINT trial (Myocardial Ischemia and Transfusion), 3504 patients with MI and anemia (hemoglobin <10 g/dL) were randomized to a restrictive (hemoglobin <8 g/dL) or liberal (hemoglobin <10 g/dL) transfusion strategy. We compared the effects of transfusion strategy on outcomes among patients with and without baseline HF. The primary outcome was death or HF at 30 days. RESULTS:Compared with patients without baseline HF (n=1633), those with baseline HF (n=1871) had higher rates of death or HF (18.0% versus 10.0%) at 30 days. Restrictive transfusion resulted in numerically higher rates of death or HF (rate ratio, 1.20 [95% CI, 0.99-1.45] versus 0.94 [95% CI, 0.70-1.26]; Pinteraction=0.18) in patients with than in those without baseline HF. Among secondary outcomes, death or recurrent MI and death were more frequent among those with baseline HF. Restrictive transfusion resulted in numerically higher rates of death or MI and death in patients with than in those without baseline HF. Rates of HF were similar between restrictive and liberal transfusion in patients with baseline HF but lower with restrictive transfusion (rate ratio, 0.51 [95% CI, 0.29-0.92]; Pinteraction=0.02) in patients without baseline HF. CONCLUSIONS:A liberal transfusion strategy is safe for patients with MI and anemia, including those with baseline HF. Restrictive transfusion tended to result in worse outcomes, particularly in patients with baseline HF. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.

Both myocardial infarction (MI) and anemia have deleterious effects on health-related quality of life (QOL). Red blood cell (RBC) transfusion may improve QOL after MI by relieving symptoms and/or increasing functional capacity. To evaluate whether a liberal transfusion strategy compared with a more restrictive transfusion strategy affects QOL in patients with MI and anemia. This analysis of QOL as a prespecified secondary outcome of the Myocardial Ischemia and Transfusion (MINT) trial, a randomized clinical trial comparing a liberal vs restrictive RBC transfusion strategy, included participants from 144 sites across 6 countries. Hospitalized adults with acute MI and anemia (hemoglobin [Hb] less than 10 g/dL). The MINT trial randomized 3504 patients, and this analysis included those who had QOL data collected and those who died before the 30-day follow-up period. Data were collected from April 2017 to April 2023, and data were analyzed from February 2024 to January 2025. The MINT trial randomized patients to a restrictive (Hb of 7 to 8 g/dL) or a liberal (Hb of less than 10 g/dL) RBC transfusion strategy. QOL was measured using the EQ-5D-5L 30 days after randomization. Of 2844 included patients, 1551 (54.5%) were male, and the mean (SD) age was 71.9 (11.5) years. A total of 2525 (88.8%; 1254 [49.7%] in the restrictive group and 1271 [50.3%] in the liberal group) had QOL data, and 319 (11.2%) died before 30-day follow-up. Overall, there were no differences in mean or median scores for any EQ-5D-5L QOL outcome between assigned transfusion strategies at 30 days postrandomization. Although a higher percentage of patients in the liberal compared with the restrictive transfusion group reported no problems compared with any problem in usual activities (506 of 1268 [39.9%] vs 473 of 1247 [37.9%]), mobility (474 of 1270 [37.3%] vs 460 of 1254 [36.7%]), and self-care (858 of 1271 [67.5%] vs 803 of 1254 [64.0%]) domains, none of these differences were statistically significant. Adjusted mixed-effects linear regressions showed no association between assigned transfusion strategy and mean differences in any QOL outcome. Adjusted regressions in several prespecified subgroups showed an association between a liberal transfusion strategy and better QOL scores in domains related to functional capacity, but the effects were only statistically significant in patients with a history of heart failure (Health Today rating: β, 2.06 [95% CI, −0.23 to 4.35] vs −1.44 [95% CI, −3.81 to 0.92]; P = .04). This secondary analysis of the MINT trial found that in patients with MI and anemia, a liberal transfusion strategy compared with a restrictive transfusion strategy did not affect QOL outcomes 30 days after randomization. This suggests that higher Hb levels maintained with RBC transfusion may not offer significant benefits to QOL overall in patients with MI and anemia. Additional studies may be useful for further examining and validating transfusion’s effect on QOL in patients with MI and heart failure. ClinicalTrials.gov Identifier: NCT02981407

BACKGROUND:The MINT trial (Myocardial Ischemia and Transfusion; N=3504) randomized patients with acute myocardial infarction (MI) and hemoglobin ≤10 g/dL to liberal (maintain hemoglobin ≥10 g/dL) or restrictive (maintain hemoglobin ≥8 g/dL) red blood cell transfusion. The results suggested a benefit on 30-day death or MI with a liberal transfusion strategy. The effect of transfusion in patients with acute MI undergoing revascularization is unclear. METHODS:In this prespecified analysis of the MINT trial, patients who underwent revascularization (n=1002) before randomization but during index hospitalization were compared with those who did not (n=2442). The primary outcome was 30-day death or MI; secondary outcomes included 30-day death, recurrent MI, the composite of death, recurrent MI, ischemia-driven unscheduled revascularization, or readmission for ischemic cardiac diagnosis, heart failure, and cardiac death. Multivariable log-binomial regression was used to determine the relative risks of the primary and secondary outcomes by transfusion strategy for revascularized and nonrevascularized patients with interaction terms. RESULTS:Patients undergoing revascularization were younger, more often female, and had fewer comorbidities than those who did not. There was no significant interaction between revascularization and assigned transfusion strategy for any outcome except cardiac death. Compared with liberal transfusion, restrictive transfusion increased the risk of 30-day cardiac death among nonrevascularized patients (relative risk, 2.45 [1.58-3.81]) but not among revascularized patients (relative risk, 0.97 [0.59,-1.60]; interaction P=0.006). CONCLUSIONS:In this analysis of the MINT trial, revascularization did not alter the effect of the randomized transfusion strategy on 30-day death or MI. The hypothesis-generating finding that a restrictive transfusion strategy was associated with an increased risk of cardiac death among patients with anemia and acute MI who do not undergo revascularization requires confirmation. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.

Importance:Both myocardial infarction (MI) and anemia have deleterious effects on health-related quality of life (QOL). Red blood cell (RBC) transfusion may improve QOL after MI by relieving symptoms and/or increasing functional capacity. Objective:To evaluate whether a liberal transfusion strategy compared with a more restrictive transfusion strategy affects QOL in patients with MI and anemia. Design, Setting, and Participants:This analysis of QOL as a prespecified secondary outcome of the Myocardial Ischemia and Transfusion (MINT) trial, a randomized clinical trial comparing a liberal vs restrictive RBC transfusion strategy, included participants from 144 sites across 6 countries. Hospitalized adults with acute MI and anemia (hemoglobin [Hb] less than 10 g/dL). The MINT trial randomized 3504 patients, and this analysis included those who had QOL data collected and those who died before the 30-day follow-up period. Data were collected from April 2017 to April 2023, and data were analyzed from February 2024 to January 2025. Interventions:The MINT trial randomized patients to a restrictive (Hb of 7 to 8 g/dL) or a liberal (Hb of less than 10 g/dL) RBC transfusion strategy. Main Outcomes and Measures:QOL was measured using the EQ-5D-5L 30 days after randomization. Results:Of 2844 included patients, 1551 (54.5%) were male, and the mean (SD) age was 71.9 (11.5) years. A total of 2525 (88.8%; 1254 [49.7%] in the restrictive group and 1271 [50.3%] in the liberal group) had QOL data, and 319 (11.2%) died before 30-day follow-up. Overall, there were no differences in mean or median scores for any EQ-5D-5L QOL outcome between assigned transfusion strategies at 30 days postrandomization. Although a higher percentage of patients in the liberal compared with the restrictive transfusion group reported no problems compared with any problem in usual activities (506 of 1268 [39.9%] vs 473 of 1247 [37.9%]), mobility (474 of 1270 [37.3%] vs 460 of 1254 [36.7%]), and self-care (858 of 1271 [67.5%] vs 803 of 1254 [64.0%]) domains, none of these differences were statistically significant. Adjusted mixed-effects linear regressions showed no association between assigned transfusion strategy and mean differences in any QOL outcome. Adjusted regressions in several prespecified subgroups showed an association between a liberal transfusion strategy and better QOL scores in domains related to functional capacity, but the effects were only statistically significant in patients with a history of heart failure (Health Today rating: β, 2.06 [95% CI, -0.23 to 4.35] vs -1.44 [95% CI, -3.81 to 0.92]; P = .04). Conclusions and Relevance:This secondary analysis of the MINT trial found that in patients with MI and anemia, a liberal transfusion strategy compared with a restrictive transfusion strategy did not affect QOL outcomes 30 days after randomization. This suggests that higher Hb levels maintained with RBC transfusion may not offer significant benefits to QOL overall in patients with MI and anemia. Additional studies may be useful for further examining and validating transfusion's effect on QOL in patients with MI and heart failure. Trial Registration:ClinicalTrials.gov Identifier: NCT02981407.

BACKGROUND:Risk-benefit tradeoffs between restrictive versus liberal red blood cell transfusion strategies may vary across individuals. This exploratory analysis aimed to derive and evaluate individualized treatment effects of defined transfusion strategies in patients with acute MI and anemia with the goal of minimizing adverse cardiovascular outcomes. METHODS:This study analyzed 3,447 (98.4%) patients randomized in the MINT (Myocardial Ischemia and Transfusion) trial between April 2017 to April 2023. Outcomes for this analysis included 30-day death or recurrent MI, death, and major adverse cardiovascular events (MACE, a composite of death, MI, stroke, and ischemia-driven unscheduled revascularization). Machine learning methods were used to identify baseline patient characteristics that informed the individualized treatment effect of a restrictive versus liberal transfusion strategy for each patient. The expected population risk of an outcome under a scenario in which patients received their optimal treatment, as indicated by the individualized treatment effect, was contrasted with expected risks for universally applying a restrictive strategy or a liberal strategy to all patients. RESULTS:Baseline characteristics did not inform individualized treatment effects on 30-day death and death or MI, suggesting minimal heterogeneity in treatment effect on these outcomes. An algorithm for estimating the individualized treatment effect on 30-day MACE included 12 baseline factors. If all patients received the optimal treatment as indicated by their estimated individualized treatment effect, the predicted risk of 30-day MACE in the sample population was 15.2% (95% CI 14.2%-16.2%). This corresponded to 4.0 (difference: -4.0%, 95% CI -5.8, -2.1) and 2.3 (difference: -2.3%, 95% CI -3.7, -0.9) percentage point risk reductions compared to applying a restrictive or liberal strategy to everyone respectively. CONCLUSIONS:The MINT trial average treatment effect, favoring a liberal strategy, may be optimal to minimize risk of 30-day death and death or MI for acute MI patients with anemia represented in the MINT sample as no individualized treatment effects were estimated on these outcomes. However, individualized transfusion strategy decisions have potential to reduce risk of 30-day MACE. External validation of the MACE algorithm is required before clinical use. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02981407, https://clinicaltrials.gov/study/NCT02981407.

BACKGROUND:The aim of this analysis was to quantify and compare the frequency of transfusion-related adverse events (TRAE) in adult patients with myocardial infarction transfused with a restrictive versus liberal transfusion strategy from the Myocardial Ischemia and Transfusion (MINT) trial. STUDY DESIGN AND METHODS:Clinical sites reported TRAE. Major TRAE were transfusion-related acute lung injury, transfusion-associated circulatory overload, acute hemolytic transfusion reaction, anaphylactic transfusion reaction, and transfusion-associated sepsis. TRAE rates per transfusion arm per patient and per 100 units of red blood cells (RBC) transfused were calculated. RESULTS:There were nine site-reported events in the restrictive transfusion arm and 49 events in the liberal transfusion arm with an overall event rate of 0.51 in the restrictive transfusion arm, and 2.80 in the liberal transfusion arm per 100 patients, rate difference -2.29; 95% confidence interval [CI], -3.12,-1.44.. The rate of major TRAE was 0.51 in the restrictive arm and 1.99 in the liberal arm per 100 patients, rate difference -1.48 (95% CI, -2.21, -0.74). When the rates were normalized per 100 units of RBC transfused, the rate difference of major TRAE was -0.08 (95% CI, -0.63, 0.46) and rate ratio was 0.90 (95% CI, 0.43, 1.87). CONCLUSION:The rate of major TRAE was low, albeit increased in the liberal transfusion arm proportional to the number of RBC units transfused. The higher rate of major TRAE in the liberal arm was not sufficient to offset the increased rates of myocardial infarction or death at 30 days observed in patients assigned to the restrictive transfusion arm.

With waning immunity and vaccine hesitancy, the COVID-19 pandemic continues to pose risks. A live microbial consortium (OL-1) with bacteria containing potentially cross-reactive antigens (CRAGs) stimulates anti-SARS-CoV-2 immune responses in vitro/vivo. We evaluated OL-1’s efficacy in enhancing anti-SARS-CoV-2 immunity in unvaccinated, previously infected adults. We conducted a pilot, parallel-group, triple-blind randomized controlled trial in 2021–2022 involving 52 generally healthy adults ages 18–60, unvaccinated against COVID-19, with SARS-CoV-2 infection ≥ 4 months prior. Participants received 21 days of either standard-dose OL-1, high-dose OL-1, or placebo. The primary outcome was change in plasma anti-SARS-CoV-2 IgG titers from baseline to Day 21. Secondary efficacy outcomes included changes through Day 42, interferon gamma (IFNg) release from stimulated peripheral blood mononuclear cells, and new SARS-CoV-2 infections. Safety was assessed through adverse events. Significant increases in plasma IgG levels were observed by Day 42 in the standard-dose OL-1 group (n = 17) compared to placebo (n = 18) (p = 0.02). No significant changes were observed in the high-dose group (n = 17). Marginal increases in IFNg release were observed in standard-dose recipients after stimulation with CD4+-specific CRAG and SARS-CoV-2 peptides and TLR7 ligands; only changes post-TLR7 ligand stimulation were significant. No new SARS-CoV-2 infections were detected. The most common adverse events overall were mild gastrointestinal symptoms; headaches were more frequent in OL-1 recipients. The live microbial consortium OL-1 was well-tolerated and associated with slightly increased anti-SARS-CoV-2 IgG levels in previously infected, unvaccinated adults at standard, but not high, dosage. Further research should confirm these findings and their clinical implications in larger populations. This study was registered on ClinicalTrials.gov (NCT04847349) on April 14, 2021.