MINT: Transfusion Strategies for Myocardial Infarction and Anemia (2021)

“Among patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days.”

  • The MINT Investigators

1. Publication Details

  • Trial Title: Liberal versus Restrictive Transfusion in Myocardial Infarction and Anemia
  • Citation: Carson JL, Brooks MM, Hébert PC, et al. Liberal versus Restrictive Transfusion in Myocardial Infarction and Anemia. N Engl J Med. 2023;388(13):1169-1179. DOI: 10.1056/NEJMoa2212442
  • Published: March 30, 2023, in The New England Journal of Medicine
  • Author: Jeffrey L. Carson, M.D.
  • Funding: The National Heart, Lung, and Blood Institute (NHLBI).

2. Keywords

  • Myocardial Infarction, Anemia, Red Blood Cell Transfusion, Transfusion Threshold, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with acute myocardial infarction (AMI) and anemia (hemoglobin <10 g/dL) (Population), does a liberal transfusion strategy (Intervention) compared to a restrictive transfusion strategy (Comparison) reduce the composite risk of recurrent MI or death at 30 days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Anemia is common in patients with AMI and is associated with worse outcomes. The optimal transfusion strategy in this population was a major clinical controversy. While a restrictive strategy (transfusing at a hemoglobin <7-8 g/dL) was the standard for most critically ill patients based on the TRICC trial (1999), there was a strong physiological argument that patients with acute coronary ischemia might benefit from a higher hemoglobin level to improve myocardial oxygen delivery.
  • Knowledge Gap: There was no definitive evidence from a large, adequately powered randomized controlled trial to guide transfusion decisions specifically in patients with AMI and anemia.
  • Proposed Hypothesis: The authors hypothesized that a liberal transfusion strategy would be superior to a restrictive strategy in reducing the risk of recurrent MI or death at 30 days.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, controlled trial (used to test the effectiveness of interventions).
  • Setting: 144 hospitals in the United States, Canada, France, Brazil, and New Zealand.
  • Trial Period: Enrollment ran from April 2017 to June 2022.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with an acute myocardial infarction (either STEMI or NSTEMI) and a hemoglobin level less than 10 g/dL.
    • Exclusion Criteria: Included patients with uncontrolled bleeding, those who had received a transfusion within the previous 48 hours, and those for whom transfusion was either mandated or refused by the treating physician.
  • Intervention: A liberal transfusion strategy, where patients received red blood cell transfusions to maintain a hemoglobin level of at least 10 g/dL.
  • Control: A restrictive transfusion strategy, where transfusions were withheld unless the hemoglobin level fell below 8 g/dL (or 7 g/dL at physician discretion), or if the patient developed symptoms of anemia.
  • Management Common to Both Groups: All other aspects of care for acute myocardial infarction were at the discretion of the treating clinicians according to international guidelines.
  • Power and Sample Size: The authors calculated that a sample size of 3500 patients would provide 90% power to detect a 2.5% absolute risk reduction in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 90% power means the study had a 90% chance of detecting the specified effect, which is considered very high).
  • Outcomes:
    • Primary Outcome: A composite of all-cause mortality or recurrent myocardial infarction at 30 days.
    • Secondary Outcomes: Included the individual components of the primary outcome and the incidence of heart failure.

6. Key Results

  • Enrollment and Baseline: 3504 patients were randomized (1749 to the liberal group and 1755 to the restrictive group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the primary composite outcome. The primary outcome occurred in 255 of 1749 patients (14.6%) in the liberal group and in 278 of 1755 patients (15.8%) in the restrictive group (p=0.21).
  • Secondary Outcomes: There were no significant differences between the groups in the individual rates of death or recurrent MI. The incidence of heart failure was slightly higher in the liberal-strategy group.
  • Adverse Events: The incidence of serious adverse events was similar in both groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a Cox proportional-hazards model.
  • Primary Outcome Analysis: The primary outcome was a time-to-event analysis of the composite of death or recurrent MI.
  • Key Statistic(s) Reported: Hazard Ratio (HR) for the primary outcome: 0.92 (95% CI, 0.77 to 1.09; P-value: 0.33).
  • Interpretation of Key Statistic(s):
    • Hazard Ratio (HR):
      • Formula: Conceptually, HR = (Hazard Rate in Intervention Group) / (Hazard Rate in Control Group).
      • Calculation: The paper reports the result as 0.92.
      • Clinical Meaning: An HR of 0.92 suggests a non-significant 8% lower risk of the primary outcome in the liberal-transfusion group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.77 to 1.09.
      • Clinical Meaning: Since this range crosses the line of no effect (1.0), it confirms that the result is not statistically significant. Clinically, this means the true effect could range from a 23% benefit to a 9% harm.
    • P-value: The p-value of 0.33 is much higher than the 0.05 threshold, indicating the result is not statistically significant and very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The very large, multicenter, randomized, controlled design provided high-quality evidence on a critical clinical question.
  • Generalizability: The pragmatic design and inclusion of a large, diverse population of MI patients make the findings highly generalizable to real-world practice.
  • Statistical Power: The very large sample size provided definitive power to confidently rule out even a small but clinically important mortality benefit.
  • Patient-Centered Outcomes: The primary outcome was a composite of death and recurrent MI, which are highly relevant patient-centered endpoints.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias.
  • External Validity (Generalizability): The findings are highly generalizable to the broad population of patients with AMI and anemia.
  • Other: The study was not designed to assess very restrictive hemoglobin triggers (e.g., <7 g/dL), as the protocol allowed for transfusion below 8 g/dL.

10. Conclusion of the Authors

  • The authors concluded that in patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days as compared with a restrictive strategy.

11. To Summarize

  • Impact on Current Practice: This was a landmark “negative” trial that provided definitive evidence to resolve a long-standing and important clinical controversy. It confirmed that a restrictive transfusion strategy is safe and appropriate for patients with acute myocardial infarction and anemia.
  • Specific Recommendations:
    • Patient Selection: For adult patients with acute MI and a hemoglobin level between 7 and 10 g/dL.
    • Actionable Intervention: A restrictive transfusion strategy, with a threshold for transfusion at a hemoglobin level of 7 to 8 g/dL, is the appropriate standard of care.
  • What This Trial Does NOT Mean: This trial does NOT mean that anemia is harmless in MI. It only suggests that routinely transfusing to a higher hemoglobin target (>10 g/dL) is not beneficial.
  • Implementation Caveats: The decision to transfuse should still be individualized, taking into account the patient’s symptoms and hemodynamic status, but a restrictive threshold should be the default approach.

12. Context and Related Studies

  • Building on Previous Evidence: The MINT trial (2023) was designed to definitively answer the question of the optimal transfusion strategy in AMI, a key population that was excluded from the original landmark TRICC trial (1999).
  • Influence on Subsequent Research: The definitive neutral result of this trial has been highly influential and will be central to the development of future transfusion guidelines, solidifying the role of a restrictive strategy even in this high-risk cardiac population.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial definitively answered its primary question with a clear neutral result.
  • Future Directions: The results of this trial will likely shift the focus of research towards understanding the mechanisms of harm from both anemia and transfusion in the setting of acute coronary syndromes.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a very common and important clinical dilemma for which there was no high-quality evidence and significant practice variation.
  • Methods: The very large, multicenter, pragmatic RCT design was appropriate and robust. The main methodological weakness is the open-label design, but the primary outcome was a composite of objective endpoints, which mitigates the risk of bias.
  • Results: The study reported a clear neutral finding for its primary outcome, with a narrow confidence interval centered on the null value. This provides strong evidence against a meaningful clinical benefit of a liberal transfusion strategy in this population.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable. This is a classic example of a high-quality “negative” trial that was profoundly practice-changing by providing strong evidence to confirm that a more conservative, restrictive strategy is safe and appropriate, even in a high-risk population.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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