Effect of Four Hemoglobin Transfusion Threshold Strategies in Patients With Acute Myocardial Infarction and Anemia : A Target Trial Emulation Using MINT Trial Data

Abstract

Background: The optimal hemoglobin threshold to guide red blood cell (RBC) transfusion for patients with acute myocardial infarction (MI) and anemia is uncertain.

Objective: To estimate the efficacy of 4 individual hemoglobin thresholds (<10 g/dL [<100 g/L], <9 g/dL [<90 g/L], <8 g/dL [<80 g/L], and <7 g/dL [<70 g/L]) to guide transfusion in patients with acute MI and anemia.

Design: Prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial using target trial emulation methods. (ClinicalTrials.gov: NCT02981407).

Setting: 144 clinical sites in 6 countries.

Participants: 3492 MINT trial participants with acute MI and a hemoglobin level below 10 g/dL.

Intervention: Four transfusion strategies to maintain patients' hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Protocol exceptions were permitted for specified adverse clinical events.

Measurements: Data from the MINT trial were leveraged to emulate 4 transfusion strategies and estimate per protocol effects on the composite outcome of 30-day death or recurrent MI (death/MI) and 30-day death using inverse probability weighting.

Results: The 30-day risk for death/MI was 14.8% (95% CI, 11.8% to 18.4%) for a <10-g/dL strategy, 15.1% (CI, 11.7% to 18.2%) for a <9-g/dL strategy, 15.9% (CI, 12.4% to 19.0%) for a <8-g/dL strategy, and 18.3% (CI, 14.6% to 22.0%) for a <7-g/dL strategy. Absolute risk differences and risk ratios relative to the <10-g/dL strategy for 30-day death/MI increased as thresholds decreased, although 95% CIs were wide. Findings were similar and imprecise for 30-day death.

Limitation: Unmeasured confounding may have persisted despite adjustment.

Conclusion: The 30-day risks for death/MI and death among patients with acute MI and anemia seem to increase progressively with lower hemoglobin concentration thresholds for transfusion. However, the imprecision around estimates from this target trial analysis precludes definitive conclusions about individual hemoglobin thresholds.

Primary funding source: National Heart, Lung, and Blood Institute.

Figure 1.

Examples of censoring for 12 clones (A7-A10, B7-B10, and C7-C10) of three MINT patients (Patients A, B, and C) under each of the 4 transfusion strategies, <7g/dL to <10g/dL We demonstrate the cloning and censoring procedures for the per-protocol analysis of the target trial emulation using three patients A, B, and C and their hypothetical “clones” 7-10. We assume no protocol exceptions occurred for these patients during the days shown. Patient A is censored from the <7g/dL and <8g/dL strategies for receiving a transfusion above these thresholds. Likewise, they are censored from the <9g/dL strategy for receiving a transfusion above this concentration at a later time. Their observed data is fully adherent to the <10g/dL strategy over the 3 days shown. Patient B is censored from the <10g/dL strategy at the end of Day 1 because their hemoglobin was below this threshold for 24 hours without receiving an RBC transfusion. They are then censored from the <8g/dL and <7g/dL strategies on Day 2 for receiving an RBC transfusion above these thresholds. On Day 3, this patient experienced a death or MI while they were adherent to the <9g/dL strategy only; this outcome would only count toward following this strategy and their follow-up time would end there. Patient C is censored from the <7g/dL strategy on Day 1 because they received a transfusion above this threshold. They experienced a death or MI on Day 2, so this outcome would count toward the <10g/dL, <9g/dL, and <8g/dL strategies. Their follow-up would end in all three strategies at this time. Patients contribute person-hours to the analysis of each strategy until they are first censored or experience an outcome in that strategy.

Figure 2.

Inverse-probability weighted, estimated cumulative incidence curves for (A) time to death/MI and (B) time to death for four RBC transfusion strategies over 30-days