Efficacy and Safety of Recanalization Therapy for Acute Ischemic Stroke With Large Vessel Occlusion

Background and Purpose: The optimal recanalization strategy for acute ischemic stroke with large vessel occlusion continues to be an area of active interest. Network meta-analysis can provide insight when direct comparative evidence is lacking. Methods: A systematic review of the literature using PubMed, Embase, the Cochrane Central Register of Controlled Trials, and SinoMed was performed, and a search was conducted for clinical trials on ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and StrokeCenter.org. Four independent reviewers conducted the study selection, data abstraction, and quality assessments. Results: The literature review identified 17 trials including 3236 patients and 8 ongoing clinical trials. Sample sizes ranged from 7 to 656 participants. Intravenous thrombolysis (IVT) was the most common intervention, followed by IVT plus mechanical thrombectomy (MT), IVT plus intraarterial thrombolysis, intraarterial thrombolysis alone, and MT alone. In the pooled network meta-analysis, IVT+MT was associated with a higher rate of independent functioning. In contrast, IVT was ranked as the most ineffective treatment strategy with respect to neurological functions, while direct MT was ranked as the least safe intervention with respect to all-cause mortality. Also, irrespective of assessment tools, endovascular treatment plus IVT led to higher successful recanalization rate than thrombolysis alone. Conclusions: Compared with other recanalization treatments, IVT+MT seems to be the most effective strategy, without increasing detrimental effects, for thrombolysis-eligible patients with large vessel occlusion-acute ischemic stroke. To improve the current evidentiary basis for recanalization treatment, future trials and real-world studies are warranted and should use unified definitions of symptomatic intracranial hemorrhage and recanalization.

The Chemical Optimization of Cerebral Embolectomy trial: Study protocol

Rationale The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. Aim The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. Sample size estimates A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). Methods and design We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20–30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). Study outcome(s) The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0–1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. Discussion The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.

Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions

Background and Purpose— Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods— The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results— A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P =0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P =0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P =0.29) and mortality (42.9% versus 44.7%; P =0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P =0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P =0.02). Conclusions— Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.

Outcomes and Complications after Intraarterial Thrombolysis for Limb Ischemia: a 4 Year Study at a Single Centre

SummaryIntroduction.The reason for using thrombolytic therapy is to eliminate vascular thrombosis and promote vascular permeability. Acute limb ischemia is associated with significant morbidity and mortality. ROCHESTER, STILE and TOPAS studies showed that thrombolytic therapy for acute limb ischemia decreases the rate of surgical interventions and significantly increases the rate of limb salvage.Aim of the Study.The purpose of this study is to assess the efficacy and outcomes of intra-arterial thrombolysis in the treatment of acute occlusions of the lower limb over a four-year period.Material and Methods.We analysed 103 patients who had been treated in our department. There were acute ischemias of stage IIa and IIb according to the Rutherford classification. The data prior to, and after thrombolysis was analysed. We usedAlteplaseas a thrombolytic agent (mean dose 62 mg ±23.5). Procedural success was based on angiographic and clinical outcomes. Statistics were calculated by SPSS 16.Results.The mean duration of symptoms prior to hospitalisation was 2.5 days (IQR 5-96 hours). The mean age at the time of thrombolysis was 63±11 for males 69±10 years for females. The success of intraarterial thrombolysis was defined by angiographic and clinical outcomes (successful in 86.4% and failed in 13.6%). Adjunctive angioplasty was performed on 39 (37.9%) patients, and immediate reconstructive surgery was required on 19 (18.4%) patients. The incidence of complications was 17,4 %, with the most common being-bleeding from the puncture side, the urinary tract or the gastrointestinal tract. Overall mortality was 8.7%. The women who required thrombolysis were older (p=0,034) and with a higher death rate (p=0.047). A CDT (catheter-directed thrombolysis) for an abdominal aorta thrombosis carries a significantly high mortality rate (p=0.00013). There were no statistically significant differences between the duration of symptoms and limb amputation and between other analysed data.Conclusions.Intraarterial thrombolysis is an effective treatment method in acute limb ischemia for selected patients, as long as accurate procedural monitoring is ensured. Thrombolysis often leads to the discovery of underlying vascular lesions. A CDT for an abdominal aorta thrombosis carries a significantly high mortality rate.