RESILIENT Brain Frailty
(2026)Objective
Assess whether baseline CT markers of cerebral small vessel disease (cSVD), as a surrogate for brain frailty, explain the reduced benefit of mechanical thrombectomy observed in elderly patients enrolled in the RESILIENT trial in Brazil.
Study Summary
• No benefit in patients ≥70 years (any cSVD) or in patients with cSVD score >1 at any age
• cSVD score mediated ~53% of the detrimental effect of age on 90-day mRS 0-2 (ACME -0.003, 95% CI -0.005 to 0.00, p=0.010)
• After adjustment, age was NOT independently associated with outcome (OR 0.99, p=0.28); NIHSS, MT, cSVD score, and glucose were the only independent predictors
Intervention
Post-hoc analysis of mechanical thrombectomy + guideline-based care vs guideline-based care alone (RESILIENT trial), with baseline CT-derived cSVD composite score (atrophy, leukoaraiosis, lacunes; range 0-3) as the modifier.
Inclusion Criteria
Age ≥18 with anterior circulation ICA/M1 large-vessel occlusion, treatable within 8 hours of last known well, pre-stroke mRS 0-1, NIHSS ≥8; all 221 randomized RESILIENT patients with baseline CT available were included.
Study Design
Arms: Mechanical thrombectomy + guideline-based care (n=111) vs guideline-based care alone (n=110), stratified by age (<70 vs ≥70) and cSVD score (0-1 vs >1).
Patients per Arm: MT: 111; Control: 110 (total N=221)
Outcome
• MT benefit in <70y with low cSVD (n=112): OR 4.16 (95% CI 1.6-10.4, p<0.01)
• MT in ≥70y with low cSVD (n=47): OR 0.84 (95% CI 0.20-3.53, p=0.81)
• MT in ≥70y with high cSVD (n=42): OR 0.76 (95% CI 0.12-4.63, p=0.76)
• Independent predictors of good outcome: NIHSS (OR 0.87, p<0.01), MT (OR 2.24, p=0.02), cSVD score (OR 0.57, p=0.01), glucose (OR 0.99, p=0.02)
• Mediation: cSVD accounted for ~53% of the age effect on outcome (ACME -0.003, 95% CI -0.005 to 0.00, p=0.010)
Clinical Question
Does baseline cerebral small vessel disease burden (as a surrogate for brain frailty), rather than chronological age itself, mediate the lack of thrombectomy benefit observed in older patients (≥70 years) in the Brazilian RESILIENT trial?
Bottom Line
Mechanical thrombectomy benefit was concentrated in patients <70 years with low cSVD burden (OR 4.16); cSVD burden — not chronological age — mediated roughly half the detrimental effect of age on 90-day functional outcome, suggesting biological brain frailty rather than age alone explains the lack of MT benefit seen in elderly Brazilian patients.
Major Points
- Post-hoc analysis of all 221 randomized RESILIENT trial participants with baseline CT imaging
- MT benefit was significant only in patients <70 years with cSVD score 0-1 (OR 4.16, 95% CI 1.6-10.4)
- No MT benefit seen in patients ≥70 years regardless of cSVD score, or in patients with cSVD score >1
- After multivariable adjustment, chronological age was NOT independently associated with outcome (OR 0.99, p=0.28)
- Causal mediation analysis showed cSVD accounted for ~53% of age's effect on outcome (ACME -0.003, p=0.010)
- Supports using biological brain frailty (rather than chronological age alone) for MT treatment selection in resource-limited settings
Study Design
- Study Type
- Post-hoc analysis of a randomized controlled trial
- Randomization
- Yes
- Blinding
- Open-label with blinded central outcome assessment; imaging analyst blinded to clinical/randomization data
- Sample Size
- 221
- Follow-up
- 90 days for functional outcome
- Centers
- 12
- Countries
- Brazil
Primary Outcome
Definition: Good functional outcome (mRS 0-2) at 90 days
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | - | - | - |
Limitations & Criticisms
- Post-hoc analysis; hypothesis-generating rather than confirmatory
- Modest sample size overall (n=221) and small numbers in subgroups (only 89 patients ≥70 years, 61 good outcomes)
- Wide confidence intervals in stratified subgroup analyses (some crossing OR 40+); limited statistical power
- cSVD burden was rated by a single trained neurologist using CT (not MRI); potential for rater bias and less sensitivity than MRI markers
- Chronic infarcts and larger non-lacunar infarcts were not specifically assessed
- Formal effect modification by cSVD score was not statistically significant despite consistent pattern
- Findings from Brazilian public healthcare system may not fully generalize to other high-income cohorts where age has not modified MT effect
Citation
Ann Neurol. 2026 Aug;100(2):361-369