Patient characteristics and main results of the included RCTs
| Trial | DIRECT-MT | DEVT | SKIP | Mr CLEAN-NO IV | SWIFT-DIRECT | DIRECT-SAFE |
| Number of patients (main analysis) | 654 | 234 | 204 | 539 | 408* | 293 |
| Median (IQR) age (years) | 69 (61–76) | 70 (60–78) | 74 (67–80) | 71 (61–79) | 73 (64–81, dMT group) vs 72 (65– 81) | 70 (61–78, dMT group) vs 69 (60– 79) |
| Median (IQR) NIHSS score | 17 (13–22) | 16 (12–20) | 18 (12–23) | 16 (10–20) | 17 (13–20, dMT group) vs 17 (12– 20) | 15 (11–20, dMT group) vs 15 (10– 20) |
| Median (IQR) ASPECTS | 9 (7–10) | 8 (7–9) | 8 (6–9) | 9 (8–10) | 8 (7–9) | 10 (9–10) |
| Occlusion site (%) | ICA 35% M1 52% M2 12% Tandem 10% | ICA 15% M1 82% M2 2% Tandem NA | ICA 35% M1 50% M2 15% Tandem 11% | ICA 22% M1 61% M2 16% Tandem 17% | ICA 29% M1 71% M2 0.2% Tandem 15% | ICA 22% M1 56% M2 15% Basilar artery 6% Tandem 16% |
| mRS 0–2 at 90 days | 36.5% vs 36.9% Adj OR 0.97 (0.68–1.37) | 54.3% vs 46.6% Adj OR 1.48 (0.81–2.74) | 59.4% vs 57.3% Unadj OR 1.09 (0.63–1.90†) | 49.1% vs 51.1% Adj OR 0.95 (0.65–1.39) | 56.7% vs 65.2% Unadj OR 0.70 (0.47–1.04) | 54.8% vs 60.5% Adj OR 0.75 (0.45–1.24) |
| mRS 0–1 at 90 days | 24.5% vs 22.6% Adj OR 1.09 (0.74–1.59) | 37.9% vs 31.4% Adj OR 1.38 (0.75–2.56) | 40.6% vs 44.6% Unadj OR 0.85 (0.49–1.48)† | 16.1% vs 15.4% Adj OR 1.01 (0.63–1.63) | 40% vs 43% | 42.5% vs 48.3% Adj OR 0.76 (0.64–1.24 |
| Whole range of the mRS | Adj cOR 1.07 (0.81–1.40) | Adj cOR 1.13 (0.71–1.79) | Unadj cOR 0.97 (0.60–1.57†) | Adj cOR 0.84 (0.62–1.15) | Adj cOR 0.75 (0.53–1.06) | Adj cOR 0.85 (0.56–1.28) |
| Death at 90 days | 17.8% vs 18.9% Unadj OR 0.93 (0.62–1.38)† | 17.2% vs 17.8% Unadj OR 0.96 (0.49–1.89)† | 7.9% vs 8.7% Unadj OR 0.90 (0.33–2.43) | 20.5% vs 15.8% Adj OR 1.39 (0.84–2.30) | 10.9% vs 8.2% Unadj OR 1.37 (0.71–2.67) | 15.1% vs 16.3% Adj OR 0.92 (0.46–1.84) |
| sICH (definition) | 4.3% vs 6.1% (Heidelberg) Unadj OR 0.69 (0.34–1.39)† | 6.1% vs 6.8% (Heidelberg) Unadj OR 0.88 (0.31–2.52)† | 5.9% vs 7.8% (SITS-MOST) Unadj OR 0.75 (0.25–2.24) | 5.9% vs 5.3% (Heidelberg) Adj OR 1.30 (0.60–2.81) | 1.5% vs 4.9% (modified SITS-MOST definition*) Unadj OR 0.30 (0.08–1.10) | 2.7% vs 4.8% (Definition not provided) Adj OR 0.57 (0.16–1.99) |
| Any ICH | 37.6% vs 42.3% | 21.7% vs 32.5% | 33.7% vs 50.5% Unadj OR 0.50 (0.28–0.88) | 35.9% vs 35.6% Adj OR 0.97 (0.68–1.38) | 29.3% vs 33.7% | NA |
| mTICI ≥2 b at the end of the procedure | 79.4% vs 84.5% OR 0.70 (0.47–1.06) | 88.5% vs 87.2% OR 1.14 (0.50–2.61) | 90.1% vs 93.2% Unadj OR 0.66 (0.24–1.82) | 78.7% vs 83.1% Adj OR 0.73 (0.47–1.13) | 90.5% vs 96.6% | 88.8% vs 89.0% Adj OR 0.84 (0.39–1.82) |
| First-pass complete reperfusion | NA | 44.0% vs 43.2% | NA | NA | NA | NA |
| Number of passes (median) | NA | Stent retriever passes: 1 (1–2) vs 1 (0–2) Aspiration device passes: 0 (0–1) vs 0 (0–1) | NA | NA | NA | NA |
| Distal embolization/ embolization in new territory | 10.7% vs 9.4% | Clot migration: 17.7% vs 23.9% | NA | 5.2% vs 3.3% Adj OR 1.31 (0.68–2.53) | NA | NA |
| Infarct volume at 24–36 hours | At a median follow-up time of 6 days: 36.3 vs 36.7 mL (NCCT) | NA | NA | 24 vs 17 mL | NA | NA |
| Onset-to-IVT time (median) | 177 (randomization)+7 | 176 | 100 (door)+36 (randomization)+14 (IVT) | 98 | 144 | NA |
| Onset-to-arterial puncture time (median) | 167 (randomization) +31 vs 177 (randomization)+36 | 200 vs 210 | 92 (door) +37 (randomization) +20 (puncture) vs 100 (door)+36 (randomization)+22 (puncture) | 130 vs 135 | NA | NA |
| Onset-to-reperfusion time (median) | 167 (randomization) +102 vs 177 (randomization)+96 | 289 vs 285 | NA | 188 vs 178 | NA | 231 vs 248 |
| Door-to-IVT time (median) | 59 | 61 | 36 (door to randomization)+14 (randomization-to-IVT time) | 31 | NA | NA |
| Door-to-arterial puncture time (median) | 84 vs 85.5 | 101 vs 105 | NA | 63 vs 64 | 75 vs 80 | NA |
| Door-to-reperfusion time (median) | NA | NA | NA | NA | 111 vs 117 | NA |
*Symptomatic intracranial hemorrhage at 24±6 hours post-randomization was defined as any parenchymal hematoma type 1 or 2, remote intracranial hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage associated with a ≥4-point worsening on the NIHSS within 24 hours.
†Post-hoc calculation based on published data
‡Day mRS was available for 407 patients
Adj, adjusted; ASPECTS, Alberta Stroke Program Early CT Score; cOR, common OR; CT, computed tomography; dMT, direct mechanical thrombectomy (MT alone); ICA, internal carotid artery; ICH, intracranial hemorrhage; IVT, intravenous thrombolysis with alteplase; M1, first segment of the middle cerebral artery; M2, second segment of the middle cerebral artery; MCA, middle cerebral artery; MRI, magnetic resonance imaging; mRS, modified Rankin Scale; MT, mechanical thrombectomy; mTICI, modified Treatment In Cerebral Ischemia; NA, not available; NCCT, non-contrast CT; NIHSS, National Institutes of Health Stroke Scale; PROBE, prospective randomized open blinded endpoint trial; RCT, randomized controlled clinical trial; sICH, symptomatic intracranial hemorrhage; Unadj, unadjusted.