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DUSK

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study

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Year of Publication: 2024

Authors: Mahmoud H. Mohammaden, Lorena Souza Viana, Hend Abdelhamid, ..., Raul G. Nogueira

Journal: Stroke

Citation: Stroke. 2024;55:1489–1497. DOI: 10.1161/STROKEAHA.123.045228

Link: https://www.ahajournals.org/doi/10.1161/STROKEAHA.123.045228

PDF: https://www.ahajournals.org/doi/reader/1...EAHA.123.045228

Clinical Question

Does endovascular treatment (EVT) improve clinical outcomes compared to medical management (MM) in patients with isolated distal medium vessel occlusion (DMVO) strokes?

Bottom Line

EVT did not demonstrate significant outcome differences compared to MM in patients with isolated DMVO, reinforcing clinical equipoise. However, subgroup analysis suggested a potential benefit of EVT for excellent outcome (mRS 0–1) in patients with moderate-to-severe strokes (NIHSS ≥8).

        Major Points
        No significant difference in 90-day mRS ordinal shift between EVT and MM in both multivariable and IPTW models.
Rates of good (mRS 0–2) and excellent (mRS 0–1) outcomes were not significantly different between groups.
Successful reperfusion (mTICI ≥2B) was achieved in 89.4% of EVT patients.
Subgroup analysis showed EVT was associated with higher likelihood of excellent outcome in NIHSS ≥8 patients (aOR 3.00, 95% CI 1.69–5.32; P-interaction=0.001), surviving Bonferroni correction.
Safety measures (sICH and 90-day mortality) were comparable between EVT and MM in multivariable analysis.
IPTW model unexpectedly showed lower sICH with EVT (aOR 0.46, P=0.013), likely due to large weights assigned to MM patients with sICH.
6 out of 9 sICH events in the MM group occurred in patients who did not receive IV thrombolysis.
40.8% of overall cohort received IV thrombolysis.
EVT group had higher baseline NIHSS (10 vs 6), higher age (69.4 vs 66.4), and longer time to treatment (340 vs 249 minutes).
Findings reinforce clinical equipoise and support ongoing randomized trials in DMVO.

      

Design

Study Type: Retrospective analysis of prospectively collected data (multicenter observational cohort)

Randomization:

Blinding: Unblinded; mRS assessed by experienced clinicians in an unblinded manner

Enrollment Period: January 2017 to June 2021

Follow-up Duration: 90 days

Centers: 7

Countries: USA, Spain

Sample Size: 321

Analysis: Multivariable ordinal logistic regression for mRS shift, binary logistic regression for dichotomized outcomes, inverse probability of treatment weighting (IPTW). Adjusted for age, stroke etiology, baseline NIHSS, time from LKN to imaging/treatment, occlusion site, baseline blood glucose, previous stroke, and IV thrombolysis. Bonferroni correction applied for subgroup analyses (P<0.0017). R Software v4.3.1.

Inclusion Criteria

Isolated DMVO stroke on initial CTA: MCA-M3/M4, ACA-A2/A3, or PCA-P1/P2
Baseline mRS score ≤2
Last known normal (LKN) to imaging/treatment ≤24 hours
Follow-up data available at 90 days

Exclusion Criteria

Primary proximal large vessel occlusion
Multivessel occlusion
Missing baseline mRS scores
Missing clinical variables
PCA-P3 segment occlusion (all treated with MM)
ACA-A1 occlusion (variability in classification)

Baseline Characteristics

Characteristic	Control	Active
N	142	179
Age - mean ± SD	66.4 ± 13.5 years	69.4 ± 13 years
Female	59.2%	65.9%
HTN	76.1%	81%
HLD	41.5%	37.4%
Diabetes	39.4%	33.5%
AF	24.6%	31.3%
Current smoker	26.1%	23.5%
Etiology - Cardioembolic	41.5%	53.1%
Etiology - Large vessel disease	8.5%	9.5%
Etiology - ICAD	7%	9.5%
Etiology - Others	43%	27.9%
Initial blood glucose - median [IQR]	66 [59–76] mg/dL	128 [108–151] mg/dL
Previous stroke	11.3%	16.8%
Baseline NIHSS - median [IQR]	6 [3–11]	10 [7–16]
IV thrombolysis	40.8%	41.3%
MCA-M3 occlusion	26.8%	34.1%
MCA-M4 occlusion	2.1%	4.5%
ACA-A2 occlusion	10.6%	13.4%
ACA-A3 occlusion	4.2%	2.2%
PCA-P1 occlusion	20.4%	28.5%
PCA-P2 occlusion	35.9%	17.3%
Time to imaging/treatment - median [IQR]	249 [120–629] min	340 [200–694] min
General anesthesia		16.2%
Successful reperfusion (mTICI ≥2B)		89.4%

Arms

Field	EVT	Control
Intervention	Mechanical thrombectomy (technique and devices at operator discretion) ± IV thrombolysis if eligible	Standard medical treatment including IV thrombolysis if presenting within 4.5 hours with no contraindications
Duration

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Ordinal shift in 90-day mRS (degree of disability)	Primary	Median mRS 3 [2–5]	Median mRS 3 [2–5]		IPTW: P=0.110; Multivariable: P=0.556
Good outcome (mRS 0–2 at 90 days)	Secondary	86/142 (60.6%)	96/179 (53.6%)	IPTW aOR 1.32 (95% CI 0.97–1.80); Multivariable aOR 1.39 (95% CI 0.80–2.45)	IPTW P=0.075; Multivariable P=0.244
Excellent outcome (mRS 0–1 at 90 days)	Secondary	56/120 (46.7%)	62/163 (38%)	IPTW aOR 1.32 (95% CI 0.94–1.85); Multivariable aOR 0.96 (95% CI 0.53–1.74)	IPTW P=0.098; Multivariable P=0.884
24-hour NIHSS score	Secondary	Median 3	Median 5		P=0.03
Symptomatic ICH	Adverse	9/142 (6.3%)	10/179 (5.6%)	Multivariable aOR 0.57 (95% CI 0.21–1.58); IPTW aOR 0.46 (95% CI 0.24–0.85)	Multivariable P=0.277; IPTW P=0.013
90-day Mortality	Adverse	13/142 (9.2%)	31/179 (17.3%)	Multivariable aOR 1.73 (95% CI 0.80–3.90); IPTW aOR 1.20 (95% CI 0.78–1.85)	Multivariable P=0.173; IPTW P=0.395

Subgroup Analysis

EVT had a significant treatment effect on excellent outcome (mRS 0–1) in patients with baseline NIHSS ≥8 (aOR 3.00, 95% CI 1.69–5.32) vs NIHSS <8 (aOR 0.84, 95% CI 0.51–1.40; P-interaction=0.001), surviving Bonferroni correction. A trend favoring EVT for good outcome in NIHSS ≥8 (P-interaction=0.008) did not survive Bonferroni correction. Posterior circulation DMVO showed higher mortality trend (aOR 1.87) vs anterior (aOR 0.73; P-interaction=0.034), but lost significance after Bonferroni correction. No definite treatment effect modification by age, IV thrombolysis, time to treatment, occlusion site, or mismatch volume for primary outcome.

Criticisms

Retrospective, non-randomized design with potential selection bias.
Unblinded outcome assessment (mRS).
Time of imaging acquisition unavailable in EVT group; puncture time used as surrogate.
Study not powered to detect small treatment differences.
Small sample size limited power for subgroup and safety analyses.
CTP parameters not included in IPTW model (>50% missing in each group).
No core laboratory for central adjudication of occlusion site or reperfusion rates.
Cognitive outcomes not assessed, particularly relevant for posterior circulation DMVO.
mRS may not capture all DMVO-related deficits (cognitive, visual impairments).
Decision to perform EVT vs MM was not standardized across centers.
Baseline imbalances between groups (NIHSS, age, time to treatment) despite IPTW adjustment.

Subgroup Analysis

Significant benefit of EVT was observed for excellent outcome (mRS 0–1) among patients with NIHSS ≥8 (aOR 3.00; 95% CI 1.69–5.32; P_interaction=0.001). No significant treatment effect modification was detected in other subgroups, including IV thrombolysis, age, occlusion site, and imaging mismatch volume.

Funding

None

Based on: DUSK (Stroke, 2024)

Authors: Mahmoud H. Mohammaden, Lorena Souza Viana, Hend Abdelhamid, ..., Raul G. Nogueira

Citation: Stroke. 2024;55:1489–1497. DOI: 10.1161/STROKEAHA.123.045228

Content summarized and formatted by NeuroTrials.ai.

DUSK

(2024)

Objective

To compare clinical outcomes of endovascular treatment (EVT) versus medical management (MM) for isolated distal medium vessel occlusion (DMVO) strokes.

Study Summary

• EVT showed no significant difference compared to MM in 90-day disability (mRS ordinal shift aOR 1.25, 95% CI 0.95–1.64; P=0.110) or rates of good/excellent outcomes in patients with isolated DMVO.
• Subgroup analysis suggested EVT was associated with higher likelihood of excellent outcome (mRS 0–1) in patients with NIHSS ≥8 (aOR 3.00, 95% CI 1.69–5.32; P-interaction=0.001).
• Safety was comparable between groups, reinforcing clinical equipoise and the need for ongoing randomized trials.

Intervention

Endovascular treatment (mechanical thrombectomy) vs. medical management (including IV thrombolysis when eligible)

Inclusion Criteria

Isolated DMVO stroke (MCA-M3/M4, ACA-A2/A3, PCA-P1/P2), baseline mRS ≤2, last known normal to imaging/treatment ≤24 hours, 90-day follow-up available

Study Design

Arms: EVT (mechanical thrombectomy) vs. medical management

Patients per Arm: 321 total (EVT: 179, MM: 142)

Outcome

• Primary: No significant difference in 90-day mRS ordinal shift (IPTW aOR 1.25, 95% CI 0.95–1.64; P=0.110).
• Secondary: No significant difference in good outcome (mRS 0–2: aOR 1.32, P=0.075) or excellent outcome (mRS 0–1: aOR 1.32, P=0.098).
• Safety: sICH comparable in multivariable model (aOR 0.57, P=0.277); 90-day mortality similar (aOR 1.20, P=0.395). Successful reperfusion achieved in 89.4% of EVT patients.

Bottom Line

Major Points

No significant difference in 90-day mRS ordinal shift between EVT and MM in both multivariable and IPTW models.
Rates of good (mRS 0–2) and excellent (mRS 0–1) outcomes were not significantly different between groups.
Successful reperfusion (mTICI ≥2B) was achieved in 89.4% of EVT patients.
Subgroup analysis showed EVT was associated with higher likelihood of excellent outcome in NIHSS ≥8 patients (aOR 3.00, 95% CI 1.69–5.32; P-interaction=0.001), surviving Bonferroni correction.
Safety measures (sICH and 90-day mortality) were comparable between EVT and MM in multivariable analysis.
IPTW model unexpectedly showed lower sICH with EVT (aOR 0.46, P=0.013), likely due to large weights assigned to MM patients with sICH.
6 out of 9 sICH events in the MM group occurred in patients who did not receive IV thrombolysis.
40.8% of overall cohort received IV thrombolysis.
EVT group had higher baseline NIHSS (10 vs 6), higher age (69.4 vs 66.4), and longer time to treatment (340 vs 249 minutes).
Findings reinforce clinical equipoise and support ongoing randomized trials in DMVO.

Study Design

Study Type: Retrospective analysis of prospectively collected data (multicenter observational cohort)
Randomization: No
Blinding: Unblinded; mRS assessed by experienced clinicians in an unblinded manner
Sample Size: 321
Follow-up: 90 days
Centers: 7
Countries: USA, Spain

Primary Outcome

Definition: Ordinal shift in 90-day mRS (degree of disability)

Control	Intervention	HR/OR	P-value
Median mRS 3 [2–5]	Median mRS 3 [2–5]	- (IPTW: 0.95–1.64; Multivariable: 0.74–1.75)	IPTW: P=0.110; Multivariable: P=0.556

Limitations & Criticisms

Retrospective, non-randomized design with potential selection bias.
Unblinded outcome assessment (mRS).
Time of imaging acquisition unavailable in EVT group; puncture time used as surrogate.
Study not powered to detect small treatment differences.
Small sample size limited power for subgroup and safety analyses.
CTP parameters not included in IPTW model (>50% missing in each group).
No core laboratory for central adjudication of occlusion site or reperfusion rates.
Cognitive outcomes not assessed, particularly relevant for posterior circulation DMVO.
mRS may not capture all DMVO-related deficits (cognitive, visual impairments).
Decision to perform EVT vs MM was not standardized across centers.
Baseline imbalances between groups (NIHSS, age, time to treatment) despite IPTW adjustment.

Citation

Stroke. 2024;55:1489–1497. DOI: 10.1161/STROKEAHA.123.045228

View Original Publication →

DUSK

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Subgroup Analysis

Funding

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