Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone

Abstract

Background and Purpose-Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear. Methods-THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany). Results-Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed. Conclusions-THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350.

Risk of Intracranial Hemorrhage after Endovascular Treatment for Acute Ischemic Stroke: Systematic Review and Meta-Analysis

“…The incidences of symptomatic intracranial hemorrhage in MR CLEAN [2] and THERAPY [26] were higher than those reported in SWIFT PRIME [6] and EXTEND-IA [5] which excluded patients with large ischemic core. Infarct volume was negatively related to baseline collateral status [27] and time delay from symptoms onset to recanalization [28] .…”

Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials

“…Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), 1 ESCAPE (The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), 2 SWIFT-PRIME (Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), 3 EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological DeficitsIntra Arterial) 4 THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke), 5 and REVASCAT (Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke), 6 have shown the efficacy of endovascular therapy in the treatment of patients with acute ischemic stroke. One major difference between these positive trials and the previous negative ones (such as IMS III-Interventional Management of Stroke III trial) 7 is the use of imaging biomarkers to select patients for randomization; the imaging biomarkers used for each trial varied from trial to trial (Table I in the online-only Data Supplement).…”

Emergency thrombectomy for acute ischaemic stroke: current evidence, international guidelines, and local clinical practice

“…[16][17][18] The 2016 THERAPY trial was the only randomised study to compare aspiration thrombectomy versus IV-tPA alone. 19 It was terminated prematurely with a limited sample size after publication of the positive stent retriever trials, and as such failed to demonstrate a statistically significant benefit for aspiration thrombectomy over intravenous thrombolysis alone.…”