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(2025)Objective
To assess whether patients with stroke with carotid tandem lesions undergoing endovascular treatment should undergo acute carotid stenting, and whether intravenous thrombolysis before EVT should influence this decision
Study Summary
• No significant increase in symptomatic ICH
• Treatment effect not modified by prior IVT (P interaction=0.81)
Intervention
Acute carotid stenting (with or without angioplasty) during endovascular treatment vs no acute stenting (including angioplasty alone, deferred treatment, or best medical treatment)
Inclusion Criteria
Patients with carotid tandem lesions from 6 RCTs comparing IVT+EVT vs EVT alone, presenting directly to EVT-capable centers, anterior circulation stroke, treated 2017-2021
Study Design
Arms: Acute carotid stenting during EVT vs No acute carotid stenting
Patients per Arm: 113 acute stenting vs 216 no acute stenting (329 total with tandem lesions from 2267 patients)
Outcome
• Excellent outcome (mRS 0-1): 38% vs 22% (adjusted OR 1.91, P=0.03)
• No significant difference in sICH or mortality between groups
Bottom Line
In this international individual participant data meta-analysis of patients with carotid tandem lesions randomized to EVT alone or IVT followed by EVT, acute carotid stenting during EVT was associated with better functional outcomes, and this association was not modified by prior treatment with IVT.
Major Points
- NOTE: Centers field shows 190 but Sample Size is only 329. This may reflect the parent trial (MR CLEAN-NO IV) rather than this sub-analysis. Verify against source publication.
- Individual participant data meta-analysis pooling 6 RCTs (DEVT, DIRECT-MT, SKIP, MR CLEAN-No IV, SWIFT DIRECT, DIRECT-SAFE) from Asia, Europe, and Oceania
- 340 of 2267 patients (15%) had carotid tandem lesions; 113 of 329 (34%) underwent acute carotid stenting
- Rate of acute stenting varied significantly across trials (23% to 62%), suggesting practice variation
- Acute stenting associated with better 90-day functional outcomes (adjusted cOR 1.60, 95% CI 1.03-2.47, P=0.04)
- IPTW analysis confirmed primary results (adjusted cOR 1.66, 95% CI 1.08-2.54, P=0.02)
- Excellent functional outcome (mRS 0-1) higher with stenting: 38% vs 22% (adjusted OR 1.91, P=0.03)
- Numerically higher rates of any ICH (44% vs 35%, aOR 1.30, P=0.30) and sICH (6.3% vs 3.7%, aOR 2.09, P=0.14), but not statistically significant
- No treatment effect heterogeneity between IVT+EVT group (cOR 2.07) and EVT alone group (cOR 1.21), P interaction=0.81
- Patients receiving stenting more likely male (82% vs 66%), had large artery atherosclerosis (81% vs 55%), lower atrial fibrillation rates (7% vs 21%)
- GP2B3A antagonists used more frequently with stenting (33% vs 5.1%)
- Low recurrent stroke rates in both groups (1.5% vs 2.7%)
Study Design
- Study Type
- Individual participant data meta-analysis of 6 randomized clinical trials
- Randomization
- Yes
- Blinding
- Open-label trials with blinded endpoint assessment for mRS at 90 days. Trials randomized patients to IVT+EVT vs EVT alone; acute stenting decision was at physician discretion (not randomized)
- Sample Size
- 329
- Follow-up
- 90 days
- Centers
- 190
- Countries
- China, Japan, Australia, New Zealand, Southeast Asia, Multiple European countries
Primary Outcome
Definition: Functional improvement defined as 1-point improvement in 7-level ordinal 90-day modified Rankin Scale (mRS) score assessed with mixed-effect ordinal regression models
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median mRS 3.00 (IQR 2.00-5.00) | Median mRS 2.00 (IQR 1.00-4.00) | - (Adjusted cOR 1.60 (1.03-2.47); IPTW adjusted cOR 1.66 (1.08-2.54)) | 0.04 (primary analysis); 0.02 (IPTW analysis) |
Limitations & Criticisms
- Observational nature regarding acute stenting decision (not randomized) - only randomization was for IVT+EVT vs EVT alone, introducing potential confounding by indication
- Heterogeneous definition of tandem lesions across included trials, with no detailed information about lesion cause (dissection vs atherosclerosis)
- No information on follow-up treatment strategy for tandem lesions in non-stenting group (heterogeneous control arm)
- Control group included diverse strategies: angioplasty alone, deferred treatment, or conservative management
- No data on carotid patency status or postprocedural treatments in acute stenting group
- Two trials (DEVT and SKIP) had small sample sizes with few acute stenting cases (<10), though sensitivity analysis excluding these trials showed consistent results
- Unable to determine whether stenting decision was made before or after treatment of intracranial occlusion
- No information on timing of stenting placement (before/after thrombectomy) available for 5 of 6 trials
- Patients receiving stenting had more favorable characteristics (more male, more atherosclerosis, less atrial fibrillation), despite IPTW adjustment
- Study population limited to patients presenting directly to EVT-capable centers - generalizability to transfer patients uncertain
- Most patients received alteplase; limited generalizability to tenecteplase (only 25 patients)
- IPTW analysis can only account for measured confounders - unmeasured confounding likely remains
- Wide variation in acute stenting rates across trials (23% to 62%) suggests heterogeneous practice patterns
- Relatively small number of events for safety outcomes (sICH, distal embolization, recurrent stroke), limiting power to detect differences
- No centralized imaging review or standardized definitions across all trials
Citation
Stroke. 2026;57:00–00. DOI: 10.1161/STROKEAHA.124.050117