ABSTRACT
For patients with anemia and myocardial infarction (MI), the randomized, 3,504-patient MINT trial found that a liberal transfusion threshold (10 g/dL) may be preferable to a restrictive threshold (8 g/dL) in terms of death or MI. The relative effects of liberal versus restrictive transfusion in younger and older patients are unknown. The present prespecified MINT substudy found no significant interaction between age and transfusion strategy for death or MI, heart failure, revascularization procedures, cardiac death, pulmonary embolism or deep vein thrombosis, bacteremia or pneumonia, and death at 30 and 180 days. A liberal transfusion approach appears to be safe and may be the preferred transfusion strategy in anemic patients with MI, regardless of age.
Background
For patients with anemia and myocardial infarction (MI), the MINT (Myocardial Ischemia and Transfusion) trial showed that a liberal blood transfusion strategy may be preferred over a restrictive strategy with respect to 30-day mortality and recurrent MI and is safe with respect to the risk of heart failure Previous research suggested that liberal transfusion may have greater benefit in younger patients as compared with patients over age 75 years We evaluated clinical outcomes with a restrictive versus a liberal transfusion strategy in younger and older patients with anemia and MI.
Key Points
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3504 patients with anemia and myocardial infarction were randomized to liberal (10 g/dL) or restrictive (8 g/dL) transfusion thresholds.
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This study found no interaction between patient age and transfusion threshold in terms of death or myocardial infarction or other adverse events.
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A liberal transfusion strategy appears to be safe and may be preferred among anemic patients with MI, regardless of age.
The MINT trial randomized 3,504 patients with MI and hemoglobin <10 g/dL to a restrictive or a liberal transfusion strategy during index hospitalization In the restrictive group, transfusion was permitted for hemoglobin <8 g/dL or angina uncontrolled with medications; in the liberal group, transfusion was required for hemoglobin <10 g/dL. In the present subgroup analysis, MINT trial patients were classified into four prespecified categories by age, prespecified in the overall trial design: <60, 60 to 69, 70 to 79, and 80+ years. Baseline clinical characteristics and inpatient transfusion strategy implementation were compared by age group. Outcomes of interest included 30-day death or MI, heart failure, revascularization procedures, cardiac death, pulmonary embolism or deep vein thrombosis, bacteremia or pneumonia, and death at 30 and 180 days. Unadjusted and multivariable adjusted log binomial and Cox proportional hazards models were created to account for factors known to impact clinical outcomes in this population. For each outcome, assigned treatment risk ratios with 95% confidence intervals were computed within age groups using log binomial and Cox regression models, and the significance of the interaction between age group and assigned treatment reported. Age was analyzed as a continuous variable in regression models and cubic spline models as sensitivity analyses. A two-tailed P -value <.05 was considered statistically significant.
In MINT, the average age was 72.1 (standard deviation 11.6) years, with 488 (14%) participants <60, 880 (25%) 60 to 69, 1,229 (35%) 70 to 79, and 906 (26%) 80+ years old. Age was missing for 1 participant. Male patients (55%) represented the majority in each age group. Patients <60 and 60 to 69 years old were more likely to have STEMI (25% and 21%, respectively) relative to patients 70 to 79 and 80+ (16% for both groups; P <.001 for this comparison). Comorbidities such as history of heart failure, atrial fibrillation, and hypertension were more prevalent in the older age groups. Mean BMI and proportion of current smokers were progressively lower in older age groups. Baseline factors were generally balanced by assigned treatment groups within each of the four age groups due to randomization. Regardless of age, the restrictive transfusion cohort received a median (interquartile range) of 0 (0, 1) units of red blood cells, the liberal transfusion cohort received a median of 2 (1, 3) units, and hemoglobin levels on days 0 to 3 after randomization did not differ by age group.
Overall, 30-day death or MI increased with increasing age from <60 to 70 to 79 years but was slightly lower in patients 80+ years old; using <60 years as the reference group, risk ratio (95% confidence interval) was 1.27 (0.93, 1.73) for 60 to 69 years, 1.81 (1.36-2.40) for 70 to 79 years and 1.58 (1.18-2.13) for 80+ years ( Figure 1 ). Exploratory cubic spline analyses confirmed that risk of 30-day death or MI increased with age from 35 to 75 years and remained steady from 75 to 95 years. Thirty-day death, cardiac death, and bacteremia or pneumonia exhibited similar trends, while risk of 30-day MI, heart failure, revascularization, and pulmonary embolism or deep vein thrombosis did not differ significantly by age group ( Figure 1 ). The risk of 180-day death increased from <60 years through 80+ years ( Figure 1 ). Multivariable-adjusted models yielded analogous results by age group. When considering whether the assigned treatment effect varied by age, there was no significant interaction between age group and transfusion strategy for any of the defined outcomes ( Figure 2 ). Similarly, there were no significant interactions between continuous age and assigned treatment for the clinical outcomes shown in Figure 2 ( P >.70 for all).
