Study Background and Disease Burden
Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, with anemia complicating the clinical course in a significant subset of patients. Anemia exacerbates myocardial ischemia by limiting oxygen delivery, potentially worsening outcomes. Blood transfusion is a common intervention to address anemia in these patients; however, transfusion carries risks including volume overload and precipitating heart failure (HF), especially in patients with pre-existing cardiac dysfunction. Clinical uncertainty persists regarding optimal transfusion thresholds to balance benefit and harm in this complex population. The Myocardial Ischemia and Transfusion (MINT) trial sought to elucidate the safety and efficacy of restrictive versus liberal transfusion strategies in patients with acute MI and anemia, across varying baseline HF status and MI types, while exploring individualized transfusion decision-making to minimize cardiovascular complications.
Study Design
The MINT trial was a randomized controlled study involving 3,504 patients presenting with acute MI and anemia (hemoglobin <10 g/dL). Participants were allocated to either a restrictive transfusion strategy (transfusion triggered at hemoglobin <8 g/dL) or a liberal strategy (transfusion triggered at hemoglobin <10 g/dL). Subgroup analyses examined outcomes based on baseline HF presence (n=1,871 with HF; n=1,633 without HF) and MI type (type 1 versus type 2 MI). Key endpoints included the composite of death or HF at 30 days (primary outcome), death or recurrent MI, and major adverse cardiovascular events (MACE). A subset analysis employed machine learning algorithms on baseline patient characteristics to generate individualized treatment effect predictions, aiming to optimize transfusion strategies on a per-patient basis. The trial was registered at ClinicalTrials.gov (NCT02981407).
Key Findings
Effects by Heart Failure Status:
Patients with baseline HF experienced higher rates of the primary composite outcome (death or HF) at 30 days compared to those without HF (18.0% vs. 10.0%). Restrictive transfusion was associated with numerically higher rates of death or HF in patients with HF (rate ratio 1.20; 95% CI, 0.99-1.45) compared to those without HF (rate ratio 0.94; 95% CI, 0.70-1.26), though the interaction was not statistically significant (P=0.18). Secondary outcomes such as death or recurrent MI and all-cause death were also more common among patients with baseline HF. Notably, restrictive transfusion resulted in worse outcomes in patients with baseline HF compared to those without it. Rates of HF events were comparable between restrictive and liberal strategies in patients with HF; however, among patients without baseline HF, restrictive transfusion was associated with significantly lower HF rates (rate ratio 0.51; 95% CI, 0.29-0.92; P=0.02).
Effects by MI Type:
In type 1 MI patients (n=1,460), the primary endpoint of death or MI was higher with restrictive transfusion (18.2%) than liberal transfusion (13.8%) (relative risk 1.32; 95% CI, 1.04-1.67). Conversely, type 2 MI patients (n=1,955) showed no significant difference between restrictive (15.8%) and liberal (15.1%) transfusion (RR 1.05; 95% CI, 0.85-1.29). Although these findings suggest a greater detrimental impact of restrictive transfusion in type 1 MI, the statistical test for interaction by MI type was not significant (P=0.16).
Individualized Transfusion Strategy Analysis:
Analysis of 3,447 patients using machine learning did not identify significant heterogeneity in treatment effect on 30-day death or death/MI, indicating a broadly favorable effect for liberal transfusion in these outcomes. For 30-day MACE, an algorithm incorporating 12 baseline variables estimated individualized treatment effects. Application of these individualized transfusion strategies could reduce MACE risk to 15.2% from risks associated with universal restrictive (19.2%) or liberal (17.5%) strategies, translating into relative risk reductions of 4.0% and 2.3%, respectively. This supports potential benefits of tailoring transfusion approaches, but external validation of this predictive model is needed before routine clinical implementation.
Expert Commentary
These findings reinforce the safety of liberal transfusion strategies in the context of acute MI complicated by anemia, particularly for patients with underlying HF who are vulnerable to adverse hemodynamic effects of anemia and transfusion triggers. The numerical trend towards worse outcomes with restrictive transfusion in this subgroup challenges the paradigm favoring conservative transfusion thresholds universally. Differences in effect size between type 1 and type 2 MI indicate pathophysiological heterogeneity—type 1 MI, driven by atherothrombotic events, may be more sensitive to oxygen delivery and anemia correction than type 2 MI, which often involves supply-demand mismatch.
Yet, the lack of strong statistical interaction and overlapping confidence intervals highlight the need for cautious interpretation. The study’s robust sample size, randomized design, and inclusion of diverse MI subtypes enhance generalizability. Limitations include the open-label design, potential unmeasured confounding, and limited follow-up duration. The innovative use of machine learning algorithms to individualize transfusion decisions heralds a shift towards precision cardiovascular medicine, although prospective validation and integration into clinical pathways remain forthcoming challenges.
Conclusion
The MINT trial provides compelling evidence supporting liberal blood transfusion strategies in patients with acute MI and anemia, including those with baseline heart failure. Restrictive transfusion policies may confer higher risks, particularly related to death, recurrent MI, and heart failure exacerbations in patients with pre-existing cardiac dysfunction. Individualized transfusion strategies hold promise to further optimize outcomes, but require additional validation. Clinicians should consider a liberal transfusion threshold, especially in type 1 MI or patients with baseline HF, balancing transfusion risks and benefits. These findings contribute significantly to guideline considerations and clinical decision-making in this high-risk population, aiming to improve cardiovascular outcomes through tailored anemia management.
