SAHARA
Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage
Year of Publication: 2025
Authors: S.W. English, A. Delaney, D.A. Fergusson, ..., for the SAHARA Trial Investigators on behalf of the Canadian Critical Care Trials Group*
Journal: N Engl J Med
Citation: N Engl J Med 2025;392:1079-88. DOI: 10.1056/NEJMoa2410962
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2410962
PDF: https://www.researchgate.net/publication...mxpY2F0aW9uIn19
PDF: Clinical Question
Does a liberal red-cell transfusion strategy, as compared with a restrictive strategy, result in a lower risk of an unfavorable neurologic outcome at 12 months in critically ill adults with acute aneurysmal subarachnoid hemorrhage and anemia?
Bottom Line
In patients with aneurysmal subarachnoid hemorrhage and anemia, a liberal transfusion strategy did not result in a lower risk of an unfavorable neurologic outcome at 12 months than a restrictive strategy. The incidence of adverse events was similar between the two groups.
Major Points
- The SAHARA trial was an investigator-initiated, pragmatic, open-label, randomized trial with a blinded outcome assessment.
- A total of 742 patients were randomized at 23 centers across Canada, Australia, and the United States.
- The primary outcome was an unfavorable neurologic outcome (modified Rankin scale score ≥4) at 12 months.
- An unfavorable neurologic outcome occurred in 33.5% of the liberal-strategy group and 37.7% of the restrictive-strategy group (risk ratio, 0.88; 95% CI, 0.72 to 1.09; P=0.22).
- Secondary outcomes, including functional independence (FIM score), quality of life (EQ-5D-5L utility index, VAS score), and mortality, did not show significant differences between groups.
- Radiographic vasospasm was observed in 31.5% of the liberal-strategy group and 40.7% of the restrictive-strategy group (risk ratio, 0.77; 95% CI, 0.63 to 0.95).
- The incidence of delayed cerebral ischemia and new cerebral infarction was similar in both groups.
- Red-cell transfusions were received by 99.7% of the liberal-strategy group and 34.9% of the restrictive-strategy group.
Design
Study Type: Randomized Controlled Trial
Randomization: 1
Blinding: Blinded outcome assessment by independent assessors who were unaware of trial-group assignments.
Enrollment Period: Pilot trial: October 17, 2015, to November 21, 2016; Full trial: March 11, 2018, to July 10, 2023.
Follow-up Duration: 12 months
Centers: 23
Countries: Canada, Australia, United States
Sample Size: 742
Analysis: Intention-to-treat. Primary outcome analyzed using a binomial generalized linear mixed model with fixed effects for treatment and sex and a random effect for center (log-link function). Proportional-odds analysis also conducted. Secondary outcomes analyzed using linear generalized linear mixed model with an identity-link function. SAS software, version 9.4; R software, version 4.3.1.
Inclusion Criteria
- Patients 18 years of age or older.
- First-ever aneurysmal subarachnoid hemorrhage.
- Hemoglobin level of ≤10 g per deciliter.
- Within the first 10 days after admission (pilot trial: within first 14 days).
Exclusion Criteria
- Nonaneurysmal subarachnoid hemorrhage.
- Active bleeding leading to hemodynamic instability.
- Contraindications to blood transfusion.
- Known objections to blood transfusion.
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Age - yr Mean | 59.3±12.5 | 59.5±12.2 |
| Age - yr Median (IQR) | 60 (51-68) | 60 (52-68) |
| Sex - Female no. (%) | 299 (81.7) | 299 (81.7) |
| Sex - Male no. (%) | 67 (18.3) | 67 (18.3) |
| Hypertension no. (%) | 161 (44.0) | 177 (48.4) |
| Current or previous smoker no. (%) | 123 (33.6) | 149 (40.7) |
| Ischemic heart disease no. (%) | 3 (0.8) | 3 (0.8) |
| Congestive heart failure no. (%) | 15 (4.1) | 28 (7.7) |
| History of intracranial hemorrhage no. (%) | 1 (0.3) | 5 (1.4) |
| Ischemic stroke no. (%) | 7 (1.9) | 14 (3.8) |
| End-stage renal disease no. (%) | 1 (0.3) | 0 |
| Chronic anemia no. (%) | 20 (5.5) | 23 (6.3) |
| No. of days from first hospital presentation to randomization Mean | 3.6±2.2 | 3.8±2.5 |
| No. of days from first hospital presentation to randomization Median (IQR) | 3 (2-5) | 3 (2-5) |
| Median score on the World Federation Neurological Surgeons scale at admission (IQR) | 3 (1-4) | 3 (1-4) |
| Median score on the modified Fisher scale (IQR) | 4 (3-4) | 4 (3-4) |
| Externalized ventricular drain no. (%) | 257 (70.2) | 255 (69.7) |
| Location of aneurysm - Anterior circulation no. (%) | 328 (89.6) | 310 (84.7) |
| Location of aneurysm - Posterior circulation no. (%) | 38 (10.4) | 56 (15.3) |
| Aneurysm treatment - Endovascular no. (%) | 218 (59.6) | 225 (61.5) |
| Aneurysm treatment - Neurosurgical no. (%) | 151 (41.3) | 140 (38.3) |
| Aneurysm treatment - No treatment no. (%) | 5 (1.4) | 6 (1.6) |
| Median no. of days from first hospitalization to first aneurysm treatment (IQR) | 1 (0-1) | 1 (0-1) |
| Presence of delayed cerebral ischemia or radiographic vasospasm - Delayed cerebral ischemia no. (%) | 50 (13.7) | 57 (15.6) |
| Presence of delayed cerebral ischemia or radiographic vasospasm - Radiographic vasospasm no. (%) | 134 (36.6) | 128 (35.0) |
| Vasopressor or inotropic therapy no. (%) | 180 (49.2) | 155 (42.3) |
| Previous red-cell transfusion no. (%) | 40 (10.9) | 28 (7.7) |
| Hemoglobin level at randomization - g/dl Mean | 9.4±0.6 | 9.3±0.6 |
| Hemoglobin level at randomization - g/dl Median (IQR) | 9.5 (9.1-9.8) | 9.5 (9.0-9.8) |
Arms
| Field | Liberal Strategy Group | Control |
|---|---|---|
| Intervention | Mandatory red-cell transfusion at a hemoglobin level of ≤10 g per deciliter. The assigned transfusion strategy was applied from the time of randomization to 21 days after the first hospital presentation, death, or hospital discharge, whichever came first. Patients received leukoreduced red cells, 1 unit at a time, when the specified hemoglobin threshold was met. | Optional red-cell transfusion at a hemoglobin level of ≤8 g per deciliter. The assigned transfusion strategy was applied from the time of randomization to 21 days after the first hospital presentation, death, or hospital discharge, whichever came first. Patients received leukoreduced red cells, 1 unit at a time, when the specified hemoglobin threshold was met. |
| Duration | Up to 21 days of hospitalization, death, or hospital discharge | Up to 21 days of hospitalization, death, or hospital discharge |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Unfavorable neurologic outcome at 12 months, defined as a score of 4 or higher on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). | Primary | 136/361 (37.7%) | 122/364 (33.5%) | 0.88 | 0.22 |
| 12-month Functional Independence Measure (FIM) score (total score, all patients) | Secondary | 79.8±54.5 | 82.8±54.6 | ||
| 12-month EuroQol five-dimension, five-level (EQ-5D-5L) utility index score (all patients) | Secondary | 0.5±0.4 | 0.5±0.4 | ||
| 12-month Visual Analogue Scale (VAS) score (all patients) | Secondary | 50±37.1 | 52.1±37.5 | ||
| Mortality at 12 months | Secondary | 98/361 (27.1%) | 99/364 (27.2%) | 0.99 | |
| New radiographic vasospasm | Secondary | 149/366 (40.7%) | 115/365 (31.5%) | 0.77 | |
| New cerebral infarction | Secondary | 65/366 (17.8%) | 58/365 (15.9%) | 0.89 | |
| New DCI (delayed cerebral ischemia) | Secondary | 73/366 (19.9%) | 64/365 (17.5%) | 0.88 | |
| Acute transfusion reactions | Adverse | Similar incidence | Similar incidence | ||
| Prespecified adverse events | Adverse | Similar incidence | Similar incidence |
Subgroup Analysis
Findings were consistent across prespecified subgroups for the primary outcome, including age (>55 years), sex, clinical severity (World Federation of Neurological Surgeons grade), radiographic grade (modified Fisher Scale), aneurysm securing method (neurosurgical vs. endovascular approach), and presence at baseline of delayed cerebral ischemia or radiographic vasospasm. Sensitivity analyses also showed consistent results.
Criticisms
- Open-label design, meaning clinical teams were aware of the intervention, which could introduce bias (though minimized by blinded outcome assessment).
- Ascertainment of some secondary outcomes (delayed cerebral ischemia, radiographic vasospasm, new cerebral infarction) is challenging in clinical trials due to overlapping definitions and incompletely understood pathophysiological features.
- The trial may not have been powered to detect smaller, but clinically meaningful, differences in benefit or harm.
- The study population, primarily from tertiary care centers in high-income countries, may limit generalizability to other settings.
Funding
Canadian Institutes of Health Research and others; Medical Research Futures Fund of Australia; Heart and Stroke Foundation (salary support to Dr. English).
Based on: SAHARA (N Engl J Med, 2025)
Authors: S.W. English, A. Delaney, D.A. Fergusson, ..., for the SAHARA Trial Investigators on behalf of the Canadian Critical Care Trials Group*
Citation: N Engl J Med 2025;392:1079-88. DOI: 10.1056/NEJMoa2410962
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