Intra-arterial mechanical thrombectomy stent retrievers and aspiration devices in the treatment of acute ischaemic stroke: A systematic review and meta-analysis with trial sequential analysis.

Purpose: Intra-arterial mechanical thrombectomy combined with appropriate patient selection (image-based selection of acute ischaemic stroke patients with large artery occlusion) yields improved clinical outcomes. We conducted a systematic review and meta-analysis, with trial sequential analysis to understand the benefits, risks and impact of new trials reporting in 2016 on the magnitude/certainty of the estimates for clinical effectiveness and safety of mechanical thrombectomy.
Method: Random effects' models were conducted of randomised clinical trials comparing mechanical thrombectomy (stent retriever or aspiration devices) with/without adjuvant intravenous thrombolysis with intravenous thrombolysis and other forms of best medical/supportive care in the treatment of acute ischaemic stroke. Study inclusion and risk of bias were assessed independently by two reviewers. Functional independence (modified Rankin Scale 0-2) and mortality at 90 days, including symptomatic intracranial haemorrhage rate were extracted. Trial sequential analysis established the strength of the evidence derived from the meta-analyses.
Findings: Eight trials of mechanical thrombectomy with a total sample size of 1841 (916 patients treated with mechanical thrombectomy and 925 treated without mechanical thrombectomy) fulfilled review inclusion criteria. The three most recent trials more precisely defined the effectiveness of mechanical thrombectomy (modified Rankin Scale 0 to 2; OR = 2.07, 95% CI = 1.70 to 2.51 based on data from eight trials versus OR = 2.39, 95% CI = 1.88 to 3.04 based on data from five trials). Meta-analyses showed no effect on mortality (OR = 0.81, 95% CI = 0.61 to 1.07) or symptomatic intracranial haemorrhage (OR = 1.22, 95% CI = 0.80 to 1.85) as found in analysis of first five trials. Trial sequential analysis indicated that the information size requirement was fulfilled to conclude the evidence for mechanical thrombectomy is robust.
Discussion: The impact of three recent trials on effectiveness and safety of mechanical thrombectomy was a more precise pooled effect size for functional independence. Trial sequential analysis demonstrated sufficient evidence for effectiveness and safety of mechanical thrombectomy.
Conclusion: No further trials of mechanical thrombectomy versus no mechanical thrombectomy are indicated to establish clinical effectiveness. Uncertainty remains as to whether mechanical thrombectomy reduces mortality or increases risk of symptomatic intracranial haemorrhage.
Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PW is co-PI for two randomised trials (PISTE & STABILISE) investigating different aspects of thrombectomy in acute stroke. Start-up phase of PISTE was mainly funded by Stroke Association but was also part funded by unrestricted institutional educational grants from Covidien & Codman who both manufacture devices used for stroke thrombectomy. STABILISE is part funded by Microvention. PW has also undertaken educational consultancy work within last three years for Codman & Microvention who both manufacture devices used for stroke thrombectomy. GAF is co-PI for STABILISE. GAF’s previous institution has received research grants from Boehringer Ingelheim (manufacturer of Alteplase), and honoraria from Lundbeck for stroke-related activities. GAF has also received personal remuneration for educational and advisory work from Boehringer Ingelheim and Lundbeck. GAF is supported by an NIHR Senior Investigator award. DF, GAF and PM have been involved in marketing activity for a Computerised Decision Aid for Stroke Thrombolysis (COMPASS), which may be made available for a cost payable to purchase the decision aid to cover the costs of technical maintenance and updating of the predictive equations and user interface, in accordance with user feedback and availability of new data on the effectiveness of thrombolysis.