A12 · PMID:42145087

Comparative Efficacy of Transfusion Strategies in Women and Men With Myocardial Infarction and Anemia: Prespecified Secondary Findings From the MINT Trial

Bottom line

In this prespecified secondary sex-stratified analysis of MINT, restrictive and liberal transfusion produced comparable 30-day death-or-MI outcomes in women and men (interaction P=0.60), but a borderline sex interaction for 30-day cardiac death (P=0.05) is an exploratory safety signal to interpret cautiously.

PICO at a glance

Population: Adults hospitalized with AMI and anemia enrolled in MINT (the abstract does not state the enrollment hemoglobin cutoff).
Intervention or exposure: Restrictive transfusion strategy (transfusion permitted but not required at Hb <8 g/dL; strongly recommended at Hb <7 g/dL).
Comparator: Liberal transfusion strategy (transfuse to maintain Hb ≥10 g/dL).
Outcomes: Primary: composite death or any subsequent MI within 30 days, MI adjudicated by a blinded Clinical Events Committee; secondary: 30-day heart failure, stroke, cardiac death, and 180-day all-cause mortality, each tested for a sex-by-treatment interaction.
Study design: Prespecified secondary sex-stratified analysis of MINT, a randomized trial at 144 sites in 6 countries (NCT02981407).

Clinical question and design

Anemia is common in acute myocardial infarction (AMI) and forces a bedside transfusion call with real tradeoffs: undertransfusing may worsen ischemia, overtransfusing carries volume-overload and immune risk. The parent MINT trial found broadly comparable (numerically favoring liberal) outcomes with restrictive versus liberal red-cell transfusion in AMI plus anemia. This prespecified secondary analysis asks a narrower question: does the transfusion-strategy effect differ between women and men? It is explicitly secondary and hypothesis-generating, not a new prespecified efficacy trial.

MINT randomized patients with AMI and anemia at 144 sites in 6 countries (US, Canada, France, Brazil, Australia, New Zealand; NCT02981407) to a restrictive strategy (transfusion permitted but not required at Hb <8 g/dL, strongly recommended at Hb <7 g/dL) or a liberal strategy (transfuse to maintain Hb ≥10 g/dL). This analysis stratified the full cohort (3,504 participants) by sex: 1,593 women (45.4%; 774 restrictive/819 liberal) and 1,911 men (54.6%; 975 restrictive/936 liberal) - an unusually balanced enrollment the authors contrast with ISCHEMIA's 22.8% women.

Intervention and outcomes measured

The intervention was a restrictive transfusion strategy compared against a liberal strategy. The primary outcome was the composite of death or any subsequent MI within 30 days of randomization, with MI adjudicated by a blinded Clinical Events Committee. The 30-day composite occurred in 15.7% of women and 15.7% of men overall (16.5% vs 17.1% restrictive; 14.9% vs 14.2% liberal).

Results

Restrictive-vs-liberal RRs ran the same direction for both sexes (women 1.11 [95% CI, 0.88-1.39]; men 1.21 [95% CI, 0.98-1.49]), interaction P=0.60 - no significant sex interaction for the primary outcome, supporting sex-neutral transfusion thresholds.

Safety and additional findings

Secondary composite and broader safety outcomes (heart failure, stroke, PE/DVT) also did not differ between women and men (adjusted HF RR 0.89; 95% CI, 0.68-1.16). 180-day mortality HRs were similar by sex (women 1.12 [0.89-1.39]; men 1.04 [0.86-1.26]; no significant interaction). One signal stood out: 30-day cardiac death showed a borderline sex interaction (P=0.05) - restrictive transfusion carried more than double the relative risk in men (RR 2.34; 95% CI, 1.48-3.70) versus no significant increase in women (RR 1.23; 95% CI, 0.77-1.97). Separately, women had lower 30-180-day mortality than men overall (11.0% vs 13.5%; P=0.04), a sex comparison unrelated to transfusion arm.

Uncertainty and limitations

The authors state this analysis "was not statistically powered to detect sex-by-treatment interactions and should be considered exploratory"; the cardiac-death interaction (P=0.05) carries multiple-comparisons risk and was not adjusted for post-randomization bleeding; the abstract does not state exact cardiac-death event counts by sex or arm, nor the enrollment hemoglobin threshold for anemia.

Literature review and evidence synthesis

This MINT sex-stratified analysis sits within a small, converging evidence base on transfusion strategy in AMI and anemia. A 2024 meta-analysis and trial sequential analysis in Arquivos Brasileiros de Cardiologia (PMID 39475958) pooled the same restrictive-vs-liberal comparison across trials predating and including MINT. A 2025 patient-level meta-analysis of four randomized trials in NEJM Evidence (PMID 39714935) is the specific meta-analysis this paper's own Discussion cites, noting MINT and pooled data both favor liberal transfusion on death/MI.

How this fits with the broader evidence

A living Cochrane review updated in 2025 on transfusion thresholds (PMID 41114449) supplies the broader hemoglobin-threshold evidence base this AMI-specific literature sits within. The trial's threshold definitions are the practical anchor: restrictive = transfuse only if Hb <8 g/dL (strongly recommended <7 g/dL); liberal = maintain Hb ≥10 g/dL. The Discussion notes the 2025 ACC/AHA ACS guidelines, as quoted in the source, support transfusion to Hb ≥10 g/dL below Hb 8 g/dL without a sex-specific threshold - this analysis's null primary-outcome interaction supports that uniform approach. Pharmacists do not need a different trigger for women versus men based on this evidence; the cardiac-death signal in men is a research flag, not an actionable threshold change.

ACPE UAN: 0683-0000-26-036-H01-P

Study source: PMID:42145087