Restrictive or liberal transfusion strategy in patients with acute MI and anemia: 6-month mortality in the Myocardial Ischemia and Transfusion (MINT) trial

Anemia is common in patients with acute myocardial infarction (MI) and impacts prognosis. Unlike most clinical settings in which a restrictive strategy is recommended, the optimal hemoglobin threshold for transfusion in MI patients and anemia remains uncertain(1,2,3).

From April 2017 to April 2023, the Myocardial Ischemia and Transfusion (MINT) trial (4) randomly assigned 3504 patients with acute MI and anemia (hemoglobin (Hb) <10 g/dL) to a restrictive (transfusion when the Hb ≤ 8g/dL) or liberal blood transfusion strategy (transfusion when the Hb ≤ 10g/dL). The assigned transfusion strategy was implemented throughout the index hospitalization up to 30 days. All-cause death at 6-months was a pre-specified secondary outcome (5). At 6-months, clinical sites obtained vital status and date/cause (cardiac, non-cardiac, unknown) of death by telephone follow-up, proxy or hospital records. The protocol was approved by participating institutions’ review boards or ethics committees; patients or surrogates provided written informed consent.

Cumulative incidence functions incorporating competing risks and chi-square statistics were used to compare risks of all-cause death and of cause-specific death by assigned arm. Corresponding hazards ratios (HR) and 95% confidence intervals (CIs) were estimated from Fine and Gray competing risk models with assigned transfusion strategy as the only independent variable. Patients who discontinued participation or were lost to follow-up were censored at the last date known to be alive or date of withdrawal. HRs were computed for the entire follow-up period, and a landmark analysis was conducted from 30 days to 6 months. All data and trial materials will be made publicly available at the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC; https://biolincc.nhlbi.nih.gov) by December 28, 2025, two years after publication of the primary manuscript for the Myocardial Ischemia and Transfusion Trial, as stipulated by the NIH.

Trial participants (4) had a mean age of 72.1 years, 45.5% were female, 55.8% had type 2 MI and 81.3% had non-ST elevation MI (NSTEMI). One-third had a prior history of MI, one-third had heart failure, and nearly half had renal insufficiency. At 30 days (4), the primary outcome, composite death or non-fatal MI, was numerically more frequent in the restrictive arm than in the liberal arm (16.9% vs. 14.5%, risk ratio (RR)=1.15; 95% CI, 0.99–1.34; P=0.07).

Vital status at 6 months was obtained for 3,419 (97.6%) patients. Overall, 729 patients died by 6 months, of whom 262 died from cardiac causes (35.9%), 314 from non-cardiac causes (43.1%) and 153 from unknown causes (21.0%). The proportion of deaths attributed to cardiac causes was greater in the first 30 days after randomization (48.0%) than from day 31 through 6 months (26.6%). At 6 months, 376 patients (21.7%) in the restrictive arm and 353 patients (20.5%) in the liberal arm had died (HR=1.07, 95% CI: 0.93–1.24). During the first 30 days, death occurred in 9.9% and 8.4% of the patients in the restrictive and liberal arms respectively (RR=1.19; 95% CI, 0.96–1.49)(4). Beyond 30 days, 13.1% and 13.2% of patients died in restrictive and liberal arms respectively (RR=0.99, 95% CI (0.81–1.20) Figure 1A).

Figure 1:

Cumulative Incidence Function Estimates for All-Cause Death (1A), and for Cause-Specific Death (cardiac cause of death (1B), non-cardiac cause (1C), unknow cause of death (1D) by Assigned Transfusion Strategy (Landmark).

The 6-month hazard of cardiac death was 52% greater in the restrictive arm as compared to the liberal arm (9.0% vs. 6.1%, HR=1.52; 95% CI: 1.19–1.94, p<0.001, mostly driven by events within 30 days Figure 1B), whereas rates of non-cardiac and unknown cause death had similar patterns from 0–30 days and beyond 30 days (Figure 1C, 1D, with overall HR=0.87, 95% CI: 0.70–1.08) for non-cardiac causes, and HR=0.88, 95% CI: 0.64–1.21 for unknown causes, respectively). This finding is not surprising given that blood flow impacts myocardial oxygen delivery, and thus, the restrictive strategy, with lower hemoglobin concentrations, may result in worsened myocardial ischemia.

This analysis has several limitations. Cause of death was based on clinician’s judgment and not centrally adjudicated, and the open-label design of the trial, as with all transfusion strategy trials, may have influenced the classification of cause of death. Six-month mortality was a prespecified outcome, but cause of death was not. MINT was not designed or powered to detect a difference between transfusion strategies on 6-month death. MINT also has several notable strengths. MINT is the largest transfusion strategy randomized trial in the setting of MI and included representative elderly patients with STEMI or NSTEMI, mostly type 1 and type 2 MIs, and patients with multiple comorbidities similar to routine clinical practice.

The main findings from the 6-month analysis of MINT are that overall mortality in patients with acute MI and anemia was high and did not differ by transfusion strategy. The exploratory landmark analysis showed that most of the increase in all-cause mortality in the restrictive strategy occurred in first 30-days, when cardiac death was significantly higher, and mortality was similar in both trial arms from 31 days to 6 months

Non standard Abbreviations and Acronyms

MINT trial

the Myocardial Ischemia and Transfusion trial

MI

Myocardial Infarction

Hb

Hemoglobine

HR

Hazard Ratio

CI

Confidence Interval

RR

Risk Ratio