Can you summarize the landmark Transfusion Requirements in Acute Coronary Syndromes (TRACS) trial that defined hemoglobin transfusion thresholds in acute coronary syndrome?

Landmark MINT Trial for Transfusion Thresholds in Acute Coronary Syndrome

The 2023 MINT (Myocardial Infarction and Transfusion) trial is the definitive landmark study that evaluated transfusion thresholds in acute coronary syndrome, enrolling 3,504 patients and comparing a restrictive strategy (transfuse at hemoglobin <7-8 g/dL) versus a liberal strategy (transfuse at hemoglobin <10 g/dL). 1

Trial Design and Population

• The MINT trial was a phase 3 randomized controlled trial that specifically enrolled patients with acute myocardial infarction and anemia (hemoglobin <10 g/dL), addressing the critical evidence gap identified by earlier guidelines 1
• Patients were randomized to either a restrictive transfusion strategy (hemoglobin cutoff 7-8 g/dL) or a liberal transfusion strategy (hemoglobin cutoff <10 g/dL) 1
• This was the largest trial to date examining transfusion thresholds specifically in the ACS population, with 3,504 patients included in the primary analysis 1

Key Findings on Primary Outcomes

• The primary composite outcome of myocardial infarction or death at 30 days occurred in 16.9% of patients in the restrictive-strategy group versus 14.5% in the liberal-strategy group (risk ratio 1.15,95% CI 0.99 to 1.34; P = 0.07) 1
• The liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days, but potential harms of a restrictive transfusion strategy could not be excluded 1
• Death occurred in 9.9% of patients with the restrictive strategy compared to 8.3% with the liberal strategy (risk ratio 1.19,95% CI 0.96 to 1.47) 1
• Myocardial infarction occurred in 8.5% of restrictive-strategy patients versus 7.2% of liberal-strategy patients (risk ratio 1.19,95% CI 0.94 to 1.49) 1

Transfusion Exposure and Hemoglobin Differences

• The mean number of red cell units transfused was 0.7 ± 1.6 units in the restrictive-strategy group compared to 2.5 ± 2.3 units in the liberal-strategy group, representing a 72% reduction in transfusion exposure 1
• The mean hemoglobin level was maintained 1.3 to 1.6 g/dL lower in the restrictive-strategy group compared to the liberal-strategy group on days 1 to 3 after randomization 1

Clinical Implications and Guideline Impact

• The MINT trial results support current guideline recommendations to transfuse at a hemoglobin threshold of 8 g/dL in ACS patients, as the restrictive strategy showed a non-significant trend toward worse outcomes 2, 3, 1
• The European Society of Cardiology recommends withholding transfusion unless hemoglobin decreases below 8 g/dL in ACS patients, reflecting the balance between oxygen delivery demands and transfusion risks 2, 3
• The American Association of Blood Banks noted that ACS patients were specifically excluded from earlier major transfusion trials, making MINT the first high-quality evidence in this population 4, 5

Comparison to Earlier Pilot Studies

• A 2013 pilot trial by Carson et al. (n=110) showed a trend toward benefit with liberal transfusion, with the primary outcome occurring in 10.9% of liberal-group patients versus 25.5% of restrictive-group patients (P = 0.054), and 30-day mortality significantly lower in the liberal group (1.8% vs 13.0%, P = 0.032) 6
• The MINT trial, being substantially larger with 3,504 patients versus 110 in the pilot study, provided more definitive evidence but showed less dramatic differences between strategies 6, 1

Critical Pitfalls to Avoid

• Do not apply the standard 7 g/dL threshold used in general hospitalized patients to those with acute coronary syndrome—the 8 g/dL threshold is more appropriate given the unique oxygen delivery demands of ischemic myocardium 2, 7, 3
• Do not rely solely on hemoglobin concentration without assessing symptoms, as ACS patients may develop ischemia at higher hemoglobin levels than other populations 2, 3
• Transfuse for symptoms regardless of hemoglobin level if the patient exhibits chest pain believed to be cardiac in origin, orthostatic hypotension unresponsive to fluid challenge, tachycardia unresponsive to fluid resuscitation, or signs of end-organ ischemia 2, 3

Balancing Risks in ACS Patients

• The risks of anemia in ACS include reduced oxygen delivery to ischemic myocardium, increased cardiac output demand, and potential triggering of recurrent acute coronary syndrome 2, 3
• The risks of transfusion include increased nosocomial infections, transfusion-related acute lung injury, transfusion-associated circulatory overload, and immunomodulating effects 2, 3
• The MINT trial demonstrated that while liberal transfusion did not significantly improve outcomes, the confidence intervals for harm with restrictive transfusion could not exclude clinically important differences, supporting the current 8 g/dL threshold as a reasonable compromise 1