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LASTE

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size

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Year of Publication: 2024

Authors: V. Costalat, T.G. Jovin, J.F. Albucher, ..., and C. Arquizan

Journal: The New England Journal of Medicine

Citation: N Engl J Med 2024;390:1677-89. DOI: 10.1056/NEJMoa2314063

Link: https://www.nejm.org/doi/10.1056/NEJMoa2314063

PDF: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2314063

Clinical Question

In patients with acute ischemic stroke due to occlusion of a proximal artery in the anterior circulation and a large baseline infarct with no restriction in maximum size, does endovascular thrombectomy plus medical care improve functional outcomes and mortality compared to medical care alone?

Study Overview

Objective

To evaluate the effectiveness of thrombectomy in patients with very low ASPECTS scores presenting within 6.5 hours of stroke onset.

Study Summary

Thrombectomy for LVO with very low ASPECTS (0–5) within 6.5 hours of onset improved 90-day functional outcomes and reduced mortality vs medical care alone (NNT 4), despite a higher rate of symptomatic ICH; benefit appeared consistent across prespecified subgroups, but the trial was underpowered for formal subgroup inference.

Intervention

Thrombectomy versus standard of care without thrombectomy.

Patients per Arm

333 randomized (166 thrombectomy, 167 control); 324 in intention-to-treat analysis (159 thrombectomy, 165 control).

Bottom Line

In patients with acute ischemic stroke and a large infarct, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone, despite a higher incidence of symptomatic intracerebral hemorrhage.

        Major Points
        Multicenter RCT assessing thrombectomy in patients with large infarct cores (ASPECTS ≤5), without upper limit on infarct size.
Trial stopped early due to results from other trials supporting thrombectomy in similar populations.
324 patients included in primary analysis (159 thrombectomy, 165 control).
Thrombectomy improved 90-day mRS (generalized odds ratio 1.63; 95% CI 1.29–2.06; P<0.001); NNT 4 (95% CI 3–8).
90-day mortality was lower in thrombectomy group (36.1% vs. 55.5%; adjusted RR 0.65; 95% CI 0.50–0.84).
Symptomatic ICH (Heidelberg) was more frequent with thrombectomy (9.6% vs. 5.7%; adj RR 1.73, 95% CI 0.78–4.68).
Functional independence (mRS 0–2) at 90 and 180 days was significantly higher with thrombectomy.

      

Design

Study Type: Multicenter, prospective, open-label, randomized, controlled trial with blinded outcome evaluation

Randomization: 1

Blinding: Blinded outcome evaluation by independent investigators; imaging assessed centrally by masked readers.

Enrollment Period: April 2019 through March 2022

Follow-up Duration: 90 days (primary), 180 days (secondary)

Centers: 30

Countries: France, Spain

Sample Size: 324

Analysis: Intention-to-treat; Wilcoxon–Mann–Whitney test for primary outcome; secondary analyses adjusted for prespecified covariates using multivariable models; missing data imputed; no adjustment for multiplicity

Inclusion Criteria

Age >18 years
Occlusion of intracranial ICA or M1 segment of MCA
ASPECTS ≤5 on CT/MRI (patients >80 years eligible only if ASPECTS 4–5)
NIHSS ≥6
mRS 0–1 before stroke
Randomization within 6.5 hours from onset (or within 24h if MRI DWI/FLAIR mismatch present)

Exclusion Criteria

Intracerebral hemorrhage on imaging
ASPECTS 0–3 for patients >80 years of age

Baseline Characteristics

Characteristic	Control	Active
Age - Median (IQR) - yr	74 (65–80)	73 (66–79)
Age >80 yr - no. (%)	38 (23.0)	34 (21.4)
Male sex - no. (%)	88 (53.3)	82 (51.6)
Transferred to thrombectomy-capable center - no. (%)	94 (57.0)	89 (56.0)
Modified Rankin scale score before stroke - 0 - no. (%)	129 (78.2)	130 (81.8)
Modified Rankin scale score before stroke - 1 - no. (%)	34 (20.6)	27 (17.0)
Median NIHSS score on admission (IQR)	21 (18–24)	21 (18–24)
Qualifying imaging method - MRI - no. (%)	140 (84.8)	131 (82.4)
ASPECTS - Median (IQR)	2 (1–3)	2 (1–3)
Median infarct volume at baseline (IQR) - ml	137 (106–187)	132 (104–185)
Occlusion site - ICA - no. (%)	74 (44.8)	69 (43.4)
Occlusion site - M1 - no. (%)	91 (55.2)	88 (55.3)
IV thrombolysis - no. (%)	58 (35.2)	55 (34.6)
Unknown time of onset - no. (%)	47 (28.5)	48 (30.2)

Arms

Field	Thrombectomy Group	Control
Intervention	Endovascular thrombectomy using approved devices plus standard medical care	Standard medical care alone
Duration	90 days (primary), 180 days (secondary)	90 days (primary), 180 days (secondary)

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Distribution of mRS score at 90 days (Wilcoxon–Mann–Whitney ordinal shift analysis; scores 5–6 combined). Treatment effect expressed as generalized odds ratio (not a hazard ratio).	Primary	Median mRS: 6 (IQR 4–6); N=165	Median mRS: 4 (IQR 3–6); N=159	4 (95% CI 3 to 8)	<0.001
mRS 0–2 at 90 days	Secondary	4.9% (8/164)	13.3% (21/158)	adj RR 2.39
mRS 0–3 at 90 days	Secondary	12.2% (20/164)	33.5% (53/158)	adj RR 2.62
Median mRS at 180 days	Secondary	6 (IQR 4–6)	4 (IQR 3–6)	generalized OR 1.71
mRS 0–2 at 180 days	Secondary	4.9% (8/162)	18.5% (29/157)	adj RR 3.26
mRS 0–3 at 180 days	Secondary	13.0% (21/162)	36.9% (58/157)	adj RR 2.67
Utility-weighted mRS at 90 days (mean±SD)	Secondary	0.16±0.25	0.30±0.32	adj mean diff 0.144
Utility-weighted mRS at 180 days (mean±SD)	Secondary	0.17±0.26	0.33±0.34	adj mean diff 0.164
EQ-5D-5L utility index at 90 days (mean±SD)	Secondary	0.10±0.32	0.30±0.43	standardized diff 0.51
EQ-5D-5L utility index at 180 days (mean±SD)	Secondary	0.14±0.34	0.32±0.41	standardized diff 0.51
Decompressive craniectomy within 7 days	Secondary	11.5% (19/165)	8.8% (14/159)	adj subdistribution HR 0.81
Early neurologic improvement	Secondary	11.4% (18/158)	30.7% (47/153)	adj RR 2.62
Mean change in infarct volume at 24 hr (ml)	Secondary	119.5 (107.9 to 131.1)	51.6 (39.9 to 63.2)	adj mean diff −67.9
Death from any cause at 90 days	Adverse	55.5% (91/164)	36.1% (57/158)	adj RR 0.65	<0.001
Symptomatic intracerebral hemorrhage within 24 hr (Heidelberg classification)	Adverse	5.7% (9/157)	9.6% (15/157)	adj RR 1.73
Symptomatic intracerebral hemorrhage within 24 hr (SITS-MOST criteria)	Adverse	2.5% (4/157)	3.2% (5/157)	adj RR 1.29
Early neurologic worsening	Adverse	36.1% (57/158)	32.0% (49/153)	adj RR 0.89
Procedure-related complications	Adverse	NA	11/159 (6.9%): embolization in previously uninvolved territory 1 (0.6%), arterial dissection 2 (1.3%), arterial perforation 2 (1.3%), other 6 (3.8%)

Subgroup Analysis

Overall generalized OR 1.63 (1.29–2.06); age ≤70 y 2.03 (1.36–3.03) and >70 y 1.44 (1.08–1.90); ASPECTS ≤2 1.77 (1.30–2.41) and ≥3 1.47 (1.02–2.09); baseline infarct volume <100 ml 1.44 (0.85–2.45), 100–150 ml 1.77 (1.20–2.60), >150 ml 1.58 (1.11–2.23); MRI 1.71 (1.32–2.21) vs CT 1.34 (0.78–2.30); IV thrombolysis yes 1.52 (1.01–2.28) vs no 1.69 (1.27–2.25). Paper notes the small sample size limited the power of subgroup analyses; results should not be used for hypothesis testing.

Criticisms

Trial was stopped early, reducing statistical power for some secondary outcomes.
Open-label design introduces potential for performance bias, though outcomes were adjudicated blinded.
Homogeneous study population from high-volume centers in France and Spain may limit generalizability.
Confidence intervals for secondary outcomes and subgroup analyses not adjusted for multiplicity.
Patients >80 years with ASPECTS 0–3 were excluded, so the benefit of thrombectomy in that population is unknown.

Funding

Montpellier University Hospital through an unrestricted grant from an industry consortium of medical device companies (Medtronic, Stryker, Balt Extrusion, MicroVention, and Cerenovus), which had no involvement in trial design or execution.

Based on: LASTE (The New England Journal of Medicine, 2024)