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SWIFT DIRECT

Thrombectomy Alone Versus Intravenous Alteplase Plus Thrombectomy in Patients with Stroke: A Randomized Controlled Non-Inferiority Trial

Year of Publication: 2021

Authors: Prof. Urs Fischer MD, Johannes Kaesmacher MD, Daniel Strbian MD, ..., Prof. Jeffrey L. Saver MD and Prof. Jan Gralla MD on behalf of the SWIFT DIRECT Collaborators

Journal: The Lancet

Citation: Lancet 2022; 400(10346): 104-115.

Link: https://boris.unibe.ch/171267/8/Fischer_Lancet_2022_AAM.pdf

PDF: https://boris.unibe.ch/171267/8/Fischer_Lancet_2022_AAM.pdf

Clinical Question

To determine whether stent-retriever thrombectomy alone is non-inferior to intravenous alteplase (IVT) plus stent-retriever thrombectomy for achieving good functional outcome in patients with acute ischemic stroke due to a large vessel occlusion in the anterior circulation.

Bottom Line

In this trial, thrombectomy alone was not shown to be non-inferior to standard care (intravenous alteplase plus thrombectomy) for achieving functional independence at 90 days. Furthermore, thrombectomy alone resulted in a lower rate of successful reperfusion. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients.

        Major Points
        SWIFT DIRECT was a multicenter, randomized, open-label, non-inferiority trial involving 408 patients in Europe and Canada.
Patients with large vessel occlusion stroke eligible for both IVT and thrombectomy were randomized 1:1 to thrombectomy alone or IVT plus thrombectomy.
The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days, with a non-inferiority margin of a -12% risk difference.
The primary outcome was achieved by 57% of patients in the thrombectomy-alone group and 65% in the IVT-plus-thrombectomy group.
Non-inferiority was not met, as the lower limit of the one-sided 95% CI for the adjusted risk difference was -15.1%, crossing the prespecified -12% margin.
Successful reperfusion (eTICI 2b50-3) was significantly less common in the thrombectomy-alone group compared to the combined therapy group (91% vs. 96%; P=0.047).
Safety outcomes, including symptomatic intracranial hemorrhage, were similar between the groups.

      

Design

Study Type: Multicenter, randomized, open-label, blinded-outcome, non-inferiority trial

Randomization: 1

Blinding: The trial was open-label for treatment, but the primary outcome assessment was performed by personnel blinded to the treatment allocation.

Enrollment Period: November 2017 to May 2021

Follow-up Duration: 90 days

Centers: 48

Countries: Europe, Canada

Sample Size: 408

Analysis: The primary outcome was assessed for non-inferiority in the intention-to-treat population using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a non-inferiority margin of -12%.

Inclusion Criteria

CTA- or MRA-confirmed occlusion of the intracranial internal carotid artery, the M1 segment of the middle cerebral artery, or both
Eligible to receive intravenous alteplase within 4.5 hours from the time last seen well
Could undergo thrombectomy within 75 minutes of randomization
NIHSS score of ≥5 and ≤30
Alberta Stroke Program Early CT Score (ASPECTS) of ≥4

Exclusion Criteria

Advanced dementia or significant preexisting disabilities

Baseline Characteristics

Characteristic	Control	Active
Group	Intravenous alteplase plus thrombectomy (N=207)	Thrombectomy alone (N=201)
Median age - yr (IQR)	72 (65, 81)	73 (64, 81)
Female sex - no. (%)	104 (50%)	105 (52%)
Median NIHSS score (IQR)	17 (12, 20)	17 (13, 20)
Median ASPECTS - (IQR)	8 (7, 9)	8 (7, 9)

Arms

Field	Control	Thrombectomy alone
Intervention	Standard of care: Intravenous alteplase (0.9 mg/kg, max 90 mg) administered as soon as possible, followed by thrombectomy with a Solitaire stent-retriever device.	Thrombectomy with a Solitaire stent-retriever device initiated as soon as possible, without preceding intravenous alteplase.
Duration	Single intervention	Single intervention

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Functional independence, defined as a score of 0-2 on the modified Rankin scale (mRS) at 90 days.	Primary	65% (135/207)	57% (114/201)		Non-inferiority not met
Successful reperfusion (final eTICI 2b50-3)	Secondary	96% (199/207)	91% (182/201)	Risk difference -5.1% (95% CI, -10.2 to 0.0%)	0.047
Mortality at 90 days	Secondary	9% (17/207)	11% (22/201)	Risk difference 2.3% (95% CI, -3.2 to 7.8%)	0.41
Symptomatic intracranial hemorrhage (global definition)	Adverse	3% (7/202)	2% (5/201)	Risk difference -1.0% (95% CI, -4.8 to 2.7%)	0.77

Subgroup Analysis

A hypothesis-generating analysis suggested a differential effect by age, with a significant detriment to thrombectomy alone in patients <70 years old, but this should be interpreted with caution.

Criticisms

Most patients were treated with a specific type of stent-retriever (Solitaire), so results may not be generalizable to other thrombectomy devices.
The study used a broad non-inferiority margin of -12%.
The per-protocol analysis was limited to 83% of patients.
The population was confined to patients directly admitted to comprehensive stroke centers, and results are not transferable to drip-and-ship models.
Approximately half of the patients were randomized after admission MRI, which may limit the generalizability of the data.

Funding

Medtronic and University Hospital Bern.

Based on: SWIFT DIRECT (The Lancet, 2021)