Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke

Abstract

IMPORTANCEFor patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. OBJECTIVE To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke.DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020).INTERVENTIONS A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. MAIN OUTCOMES AND MEASURESThe primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was −10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. RESULTSThe trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, −5.1% to ϱ)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, −0.8%; 95% CI, −7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, −0.5%; 95% CI, −10.3% to 9.2%).CONCLUSIONS AND RELEVANCE Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold.

Comparison of Prior Bridging Intravenous Thrombolysis With Direct Endovascular Thrombectomy for Anterior Circulation Large Vessel Occlusion: Systematic Review and Meta-Analysis

“…Moreover, some studies enrolled patients who were eligible for IVT into the direct EVT arm (17)(18)(19)(20), whereas others enrolled patients who were not eligible for IVT into direct EVT treatment (21)(22)(23)(24), which made these studies uncomparable. Recently, three RCTs have shown that bridging treatment was not superior to direct EVT for patients who were also eligible for IVT (25)(26)(27). Because of the controversies in this field regarding the application of bridging treatment (combining prior IVT and EVT) and direct EVT, a meta-analysis was needed to explore the advantages and disadvantages of both approaches of treatment in patients with IVT eligibility.…”

Low-Dose vs. Standard-Dose Intravenous Alteplase in Bridging Therapy Among Patients With Acute Ischemic Stroke: Experience From a Stroke Center in Vietnam

“…The DEVT (Direct Endovascular Thrombectomy vs. Combined IVT and Endovascular Thrombectomy for Patients With Acute Large Vessel Occlusion in the Anterior Circulation) trial in China also demonstrated the non-inferiority of primary MTE treatment over the bridging therapy (standard-dose IVT + MTE) in functional independence (noninferiority margin of 10%) (8). However, there may be individual factors in the decision-making process that were not captured in the clinical trials (2).…”

Treating acute large vessel occlusion stroke: to bridge or not to bridge?

“…The door-to-needle times of DIRECT-MT, 1 DEVT 2 and SKIP 3 were 59 (45-78) min, 61 (49-81) min and 50 min, respectively, which represent a substantial delay in relation to the 40 (29-55) min reported in the HERMES meta-analysis (Highly Effective Reperfusion Evaluated Open access in Multiple Endovascular Stroke Trials) and may have resulted in lower rates of favourable outcomes than what would have been accomplished with shorter door-toneedle times. 7 Moreover, the rates of favourable outcomes noted in DIRECT-MT 1 were significantly lower than those noted in DEVT 2 and SKIP. 3 This may be related to the differences of stroke aetiology across the trials with varying proportions of undetermined causes and intracranial atherosclerosis.…”

“…1 Likewise, the recently published DEVT (Direct Endovascular Thrombectomy vs Combined IVT and Endovascular Thrombectomy for Patients With Acute Large Vessel Occlusion in the Anterior Circulation) trial involving 234 Chinese patients who had an anterior circulation LVOS found that the rate of functional independence (90-day mRS ≥2) in dEVT group was numerically higher than that in the BT group (54.3% vs 46.6%, difference: 7.7%, 1-sided 97.5% CI: −5.1% to ∞; p=0.003 for non-inferiority). 2 With prespecified noninferiority threshold of 10% for the favourable outcome proportion difference, the trial concluded that dEVT was non-inferior to BT. 2 Simultaneously published with DEVT, the SKIP (Direct Mechanical Thrombectomy in Acute LVO Stroke) trial included 204 patients who had an acute ischaemic stroke with internal carotid artery or middle cerebral artery M1 occlusions presenting within 4.5 hours of stroke onset across 23 sites in Japan.…”

“…2 With prespecified noninferiority threshold of 10% for the favourable outcome proportion difference, the trial concluded that dEVT was non-inferior to BT. 2 Simultaneously published with DEVT, the SKIP (Direct Mechanical Thrombectomy in Acute LVO Stroke) trial included 204 patients who had an acute ischaemic stroke with internal carotid artery or middle cerebral artery M1 occlusions presenting within 4.5 hours of stroke onset across 23 sites in Japan. 3 Favourable outcome occurred in 60 patients (59.4%) in the dEVT group and 59 patients (57.3%) in the BT group, with no significant between-group difference (difference, 2.1% (1-sided 97.5% CI −11.4% to ∞); OR 1.09 (1-sided 97.5% CI 0.63 to ∞); p=0.18 for non-inferiority).…”