March 16, 2025
Endovascular Treatment for Acute Ischemic Stroke Due to Medium & Distal Vessel Occlusions: the DISTAL & ESCAPE-MeVO Trials
Key Points:
Evidence before these studies: Previous evidence supporting endovascular therapy in medium/distal vessel occlusions primarily came from observational studies or subgroup analyses of larger vessel occlusion trials, leaving uncertainty regarding the efficacy of endovascular therapy in this population.
Question:
Does endovascular therapy improve clinical outcomes compared to standard medical management in acute ischemic stroke due to medium/distal vessel occlusion?
Findings:
The randomized DISTAL (N=543) and ESCAPE-MeVO (N=530) trials found no significant benefit of endovascular therapy compared to standard medical treatment in improving functional outcomes at 90 days among patients with acute ischemic stroke due to medium or distal vessel occlusions. ESCAPE-MeVO showed a significantly higher mortality rate with endovascular therapy, and both trials noted increased rates of symptomatic intracranial hemorrhage with endovascular therapy.
Implications:
Current evidence does not support routine endovascular therapy for acute ischemic stroke caused by medium or distal vessel occlusions. Patients generally considered to benefit from endovascular therapy are those with intracranial ICA, M1 segment MCA, or basilar artery occlusion as well as proximal or dominant M2 MCA occlusion when salvageable tissue is identified by imaging.
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Background:
Acute ischemic stroke resulting from medium vessel occlusions (MeVO), involving the distal middle cerebral artery (MCA) segments (M2, M3), the anterior cerebral artery (ACA), and the posterior cerebral artery (PCA) can result in significant disability. Historically, the evidence on endovascular therapy (EVT) efficacy in MeVO has come from observational studies and subgroup analyses of large vessel occlusion (LVO) stroke trials, leaving uncertainty as to whether EVT improves clinical outcomes in these populations. The DISTAL and ESCAPE-MeVO trials were designed to determine whether EVT plus standard medical treatment confers additional benefit compared to standard medical treatment alone for acute ischemic stroke due to MeVO.
Overview of Studies & Methods
DISTAL and ESCAPE-MeVO were randomized trials with blinded endpoint assessment that evaluated the efficacy of EVT in adults experiencing acute ischemic stroke due to MeVO.
| Trial | N | Presentation Window | NIHSS Criteria | Medium/Distal Vessel Occlusion |
| DISTAL Trial | 543 | ≤24 hours | ≥4 or disabling deficit | Non-dominant or co-dominant M2, M3-M4 MCA; ACA (A1-A3); PCA (P1-P3) |
| ESCAPE-MeVO Trial | 530 | ≤12 hours | >5, or 3-5 if disabling deficit | M2-M3 MCA; A2-A3 ACA; P2-P3 PCA |
DISTAL excluded dominant M2 MCA occlusions, whereas ESCAPE-MeVO excluded A1 ACA and P1 PCA occlusions and required imaging evidence of salvageable brain tissue.
Intracranial Arterial Segments
Key Results
| Outcome | ESCAPE-MeVO | DISTAL |
| Primary outcome (functional outcome at 90 days) | No benefit (mRS 0-1): EVT 41.6% vs. usual care 43.1% (P=0.61) | No difference in disability (mRS distribution: OR 0.90; 95% CI, 0.67–1.22; p=0.50) |
| Mortality (90 days) | Significantly higher with EVT (13.3% EVT vs. 8.4% usual-care; aHR 1.82; 95% CI, 1.06–3.12) | Similar (15.5% EVT vs. 14.0% usual-care; OR 1.17; 95% CI, 0.71–1.90) |
| Symptomatic Intracranial Hemorrhage | Higher with EVT (5.4% EVT vs. 2.2% usual care) | Non-significantly higher with EVT (5.9% EVT vs. 2.6% usual care) |
| Reperfusion Rate | 75.1% | 71.7% |
- There was no clear benefit of EVT compared with medical management alone for improving functional independence or reducing disability in patients with MeVO and distal occlusions.
- Mortality was notably higher in ESCAPE-MeVO’s EVT arm and symptomatic intracranial hemorrhage rates were higher in the EVT arm in both trials.
Limitations & Future Directions
There are important limitations to consider when interpreting the results:
- Baseline Stroke Severity: Both trials enrolled patients with relatively mild deficits (median NIHSS scores: DISTAL 6; ESCAPE-MeVO 8), which could limit the measurable benefit derived from EVT.
- Participant Age: The median age of participants was higher (DISTAL: 77 years; ESCAPE-MeVO: 75 years) when compared to previous landmark LVO trials, raising concerns about potential selection bias.
- Technical Limitations & Spontaneous Recanalization: Reperfusion success rates (~71–75%) were lower compared to previous LVO trials, potentially due to technical challenges associated with interventions in smaller vessels or inherent limitations of stent retrievers in this context. ESCAPE-MeVO specifically required initial use of the Solitaire X device and DISTAL allowed any commercially available device. About 15% of the ESCAPE-MeVO EVT participants had spontaneous recanalization after initial imaging but before EVT (typically following intravenous thrombolysis), potentially influencing results.
Future meta-analyses of these trials could help identify subgroups of patients with MeVO or distal intracranial occlusion acute stroke who are more likely to benefit from EVT, which would inform the design of future clinical trials. An important concern raised by trial investigators is the impact of real-world clinical practice on trial enrollment. The treatment of patients outside of the trials (based on prior observational data suggesting potential benefit) likely led to real-world EVT treatment rather than randomized enrollment into clinical trials for the patients most likely to benefit (such as proximal M2 segment MCA occlusions, those with higher stroke severity (NIHSS), or younger patients). The loss of equipoise in clinical practice potentially led to selective exclusion of these patients from trials, thereby introducing enrollment bias, skewing trial results, and impairing accurate assessment of EVT efficacy for MeVO.
Clinical Implications
The current evidence does not support routine EVT for acute ischemic stroke caused by medium- and distal-vessel occlusions.
Patients generally considered to benefit from EVT are those with:
- Intracranial ICA, M1 segment MCA, or basilar occlusion.
- Proximal (≤1cm from bifurcation) or dominant M2 (larger caliber compared to the other M2 branch(es)) segment MCA occlusion in the horizontal segment, when there is imaging evidence of salvageable tissue.
References
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