← Back

IVT for Minor Stroke

Intravenous Alteplase Versus Best Medical Therapy for Patients With Minor Stroke: A Systematic Review and Meta-Analysis

Year of Publication: 2024

Authors: Yang Zhang; Tian Lv; Thanh N. Nguyen; Simiao Wu; Zhi Li; Xue Bai; Dan Chen; Chuansheng Zhao; Wanyi Lin; Shiqin Chen; Yi Sui

Journal: Stroke

Citation: Stroke. 2024;55:883–892. DOI: 10.1161/STROKEAHA.123.045495

Link: https://www.ahajournals.org/doi/10.1161/STROKEAHA.123.045495

PDF: https://www.ahajournals.org/doi/epub/10....EAHA.123.045495

Clinical Question

Does intravenous thrombolysis with alteplase improve functional outcomes compared with best medical therapy in patients with acute minor ischemic stroke (NIHSS 0–5)?

Bottom Line

Meta-analysis of 20 studies (13,397 patients): IVT with alteplase does NOT improve excellent outcome (mRS 0-1) vs BMT in minor stroke NIHSS ≤5 (82.89% vs 80.90%; OR 1.10; 95% CI 0.89-1.37). IVT substantially increases sICH (1.61% vs 0.12%; OR 7.48; P<0.001) and hemorrhagic transformation (6.56% vs 1.54%; OR 4.73; P<0.001). RCTs alone: OR 0.87 (0.60-1.27). No subgroup showed benefit. Supports BMT (especially DAPT) over alteplase for minor stroke.

        Major Points
        No benefit of IVT on mRS 0-1: 82.89% vs 80.90% (OR 1.10; 95% CI 0.89-1.37; P=0.274). RCTs only: OR 0.87 (0.60-1.27).
7.5x increased sICH: 1.61% vs 0.12% (OR 7.48; 95% CI 3.55-15.76; P<0.001).
4.7x increased hemorrhagic transformation: 6.56% vs 1.54% (OR 4.73; 2.40-9.34; P<0.001).
Higher early neurological deterioration: 4.81% vs 2.97% (OR 1.81; 1.17-2.80; P=0.007).
No mortality difference: 0.85% vs 1.05% (OR 0.67; 0.39-1.15).
No subgroup showed IVT benefit: nondisabling, antiplatelet comparison, LVO exclusion, time window — all consistent.
DAPT noninferior to IVT per ARAMIS and PRISMS with fewer hemorrhagic complications.
Largest meta-analysis on topic: 13,397 patients (3 RCTs + 17 observational), 20 studies.
All sICH definitions consistent: ECASS II OR 7.76, ECASS III OR 4.22, NINDS OR 10.90.
Knowledge gap: no tenecteplase or urokinase data. TEMPO-2 ongoing.

      

Design

Study Type: Systematic review and meta-analysis

Randomization:

Blinding: N/A (meta-analysis)

Enrollment Period: Literature search through August 10, 2023

Follow-up Duration: 90 days (across included studies)

Centers: Multiple (20 studies)

Countries: Multiple (China, US, Australia, etc.)

Sample Size: 13397

Analysis: Random effects (I²≥50%) or fixed effects. Adjusted ORs preferred. Stata 17.0. MOOSE + PRISMA 2020. PROSPERO CRD42023445856.

Inclusion Criteria

Adults (≥18 years) with acute minor ischemic stroke (NIHSS 0–5)
Eligible for thrombolysis within 4.5 hours after onset
Received either IV alteplase or best medical therapy
Randomized controlled trials or observational studies

Exclusion Criteria

No control group
Received endovascular thrombectomy or bridging therapy
Case reports, guidelines, reviews, or conference reports
Definitions of minor stroke or outcomes not meeting criteria
Flawed study design or low quality

Baseline Characteristics

Characteristic	Control	Active

Arms

Field	Intravenous thrombolysis (IVT)	Control
Intervention	Intravenous alteplase administered within 4.5 hours of symptom onset	Antiplatelets, anticoagulants, statins, blood pressure and glucose control, and other secondary prevention measures per guidelines (excluding IVT)
Duration

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR
Excellent functional outcome (mRS 0–1 at 90 days)	Primary	Reference	OR 1.10 (95% CI 0.89–1.37)
mRS 0–2 at 90 days	Secondary	Reference	OR 1.16 (95% CI 0.95–1.43)	1.16
Mortality	Secondary	Reference	OR 0.67 (95% CI 0.39–1.15)	0.67
Recurrent stroke	Secondary	Reference	OR 0.89 (95% CI 0.57–1.38)	0.89
Recurrent ischemic stroke	Secondary	Reference	OR 1.09 (95% CI 0.68–1.73)	1.09
Early neurological deterioration	Adverse	Reference	OR 1.81 (95% CI 1.17–2.80)	1.81
Symptomatic intracranial hemorrhage	Adverse	Reference	OR 7.48 (95% CI 3.55–15.76)	7.48
Hemorrhagic transformation	Adverse	Reference	OR 4.73 (95% CI 2.40–9.34)	4.73

Subgroup Analysis

No difference in functional outcome between IVT and BMT in patients with nondisabling deficits or those on antiplatelet therapy.

Criticisms

Heterogeneity in study designs and patient selection across included studies
Lack of patient-level data limits ability to adjust for confounders
Potential publication bias

Funding

Not specified in the main text; see funding disclosures in original article

Based on: IVT for Minor Stroke (Stroke, 2024)