REALITY
PubMed • Full text • ClinicalTrials.gov
Clinical Question
In patients with acute myocardial infarction, is a restrictive transfusion threshold (hemoglobin ≤8 g/dL) non inferior for 30-day MACE events when compared to liberal transfusion threshold (hemoglobin ≤10 g/dL)?
Bottom Line
Among patients hospitalized for an acute myocardial infarction, a restrictive transfusion threshold (hemoglobin ≤8) was non-inferior to a liberal threshold (hemoglobin ≤10) for 30 day MACE events.
Major Points
Based upon results of trials like TRICC (1999), TRISS (2014), hgb transfusion thresholds among adult patients has lowered to the ~7-8 g/dL. Observational studies have identified anemia as a risk factor for mortality among those with MI, but the role for transfusion in this population is unclear.[1] It is possible that adults with MI might have reduced coronary perfusion, which might worsen MI outcomes, for example. However, the 2015 TITRe2 trial[2] found no benefit for higher transfusion thresholds among adults undergoing cardiac surgery (about half of whom underwent CABG). Whether a restrictive transfusion threshold was non-inferior to a liberal transfusion threshold among adults with MI was unclear.
Published in 2021, the Restrictive and Liberal Transfusion Strategies in Patients With Acute Myocardial Infarction (REALITY) trial randomized 668 adults with MI to a liberal transfusion threshold (hemoglobin ≤10) or restrictive threshold (hemoglobin ≤8 g/dL). The primary outcome was MACE (death, stroke, recurrent MI, or emergency revascularization for ischemia) at 30 days. The restrictive strategy was found to be non-inferior to the more liberal transfusion strategy. During the trial, 35.7% of the restrictive group and 99.7% of the liberal transfusion group received ≤1 transfusion. Overall, this trial provides some support for the use of a restrictive transfusion strategy in stable patients hospitalized for MI.
Guidelines
As of July 2021, no guidelines have been published that reflect the results of this trial.
Design
- Multicenter, open-label randomized trial
- N=666
- Restrictive (n=342)
- Liberal (n=324)
- Setting: 35 hospitals in France and Spain
- Enrollment: 2016-2019
- Mean follow-up: 30 days
- Analysis: As-treated and as-randomized
- Primary composite outcome: MACE at 30 days (all-cause mortality, stroke recurrent MI, emergency revascularization for ischemia)
Population
Inclusion Criteria
- Acute myocardial infarction: defined by ischemic symptoms within 48 hours before admission and elevated biomarkers
- Hemoglobin 7-10 g/dL
- Age at least 18 years
Exclusion Criteria
- Shock
- MI after revascularization
- Life-threatening or massive ongoing bleeding
- Transfusion in the past 30 days
- Malignant hematologic disease
Baseline Characteristics
For restrictive group
- Demographics: Age 78 years, female sex 41%
- Race: White 88.7%, North African 8.6%, African/Caribbean 2%, Indian <1%, other Asian 0%
- MI type: NSTEMI 68%, STEMI 31.6%
- Killip class: I 56%, II 26%, III 16%, IV 2%
- History of bleeding requiring transfusion: 7%
- Chronic anemia: 1*%
- Congestive Heart Failure: 13%
- Hemoglobin at admission: 10.0
- Median duration from admission to randomization: 1.6 days
Interventions
- Randomized to an arm:
- Restrictive - Transfusion threshold of hemoglobin ≤8 g/dL
- Liberal - Transfusion threshold of hemoglobin ≤10 g/dL
Outcomes
Comparisons are restrictive vs. liberal transfusion strategies in the as-randomized analyses
Primary Outcomes
- MACE at 30 days
- Defined as all-cause mortality, stroke recurrent MI, emergency revascularization for ischemia.
- 11.1% vs 14.2% (RR 0.78; 1-sided 97.5% CI 0.00-1.17)
Secondary Outcomes
- All-cause mortality
- 5.6% vs 7.7%
- Nonfatal recurrent myocardial infarction
- 2.1% vs 3.1%
- Emergency revascularization
- 1.5% vs. 1.9%
- Nonfatal ischemic stroke
- 0.6% vs. 0.6%
Additional Outcomes
- Patients who received &g;e1 unit of packed red blood cells
- 35.7% vs 99.7%
Subgroup Analysis
No significant treatment heterogeneity by subgroups of age, sex, BMI, diabetes, hypertension, dyslipidemia, type of myocardial infarction, creatinine clearance, hemoglobin level at presentation, or identification of active bleeding.
Adverse Events
- ≥1 adverse event
- 11.7% vs 11.1%
- Acute kidney injury
- 9.7% vs 7.1%
- Acute HF
- 3.2% vs. 3.7%
- Acute lung injury/ARDS
- 0.3% vs 2.2%
- Infection
- 0% vs 1.5%
- Severe allergic reaction
- 0.9% vs 0%
Criticisms
- Open label
- Non-inferiority margin was set at a relative risk of 1.25 which some clinicians may consider to include a clinically significant harm; reassuringly, the point estimate trended toward a reduction in the primary endpoint for the restrictive group.
- Few with high Killip class symptoms
Funding
Programme de Recherche Medico-Economique 2015 and Instituto de Salud Carlos III