Comment Authors: Daniela Pimenta Silva, Diana Aguiar de Sousa, Department of Neurology, Hospital de Santa Maria, University of Lisbon, Portugal
Original Article: Flynn D., Francis R., Halvorsrud K., et al 2017. 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. European Stroke Journal. doi: 10.1177/2396987317719362
There is increasing evidence that mechanical thrombectomy (MT) achieves higher recanalization rates and better clinical outcomes than intravenous thrombolysis, with no increased risk of symptomatic intracranial haemorrhage (SICH) or mortality. Several meta-analyses of randomised controlled trials (RCTs) on the topic have been published recently, each of which has considered different inclusion criteria.
In this paper published in the in the European Stroke Journal, Flynn and colleagues1 evaluated the additional impact of the three mechanical thrombectomy trials published in 2016 on the already published data.
They included studies published by the end of 2016 and those published prior to January 2009 were excluded. Trials were eligible for the review if they included more than 10 adult patients (aged ≥ 18) presenting with acute ischaemic stroke receiving MT (stent retrievers and aspiration devices) with or without adjuvant intravenous thrombolysis (IVT) or standard medical care and those with at least one outcome assessment at ≥90 days follow-up.
The authors used Trial Sequential Analysis (TSA) to establish the reliability of data collected from recent trials.
Trial Sequential Analysis (TSA)2 is a methodology that calculates the information size (cumulated sample sizes of included trials) required for a meta-analysis to present the best available and/or sufficient evidence. It adjusts significance levels for sparse data and repetitive testing on accumulating data, thus helping to quantify the robustness of a meta-analysis.
Eight RCTs were considered eligible for inclusion in the meta-analyses. The combined sample size was 1841 (916 patients treated with MT and 925 treated without MT).
Patients treated with MT were significantly more likely to be functional independent (mRS 0 to 2) at 90-days follow-up (OR = 2.39, 95% CI).
The inclusion of the three most recent trials (THERAPY, THRACE and PISTE) caused slightly decreased pooled effect size (OR 2.07 vs 2.39), but with increased certainty, as shown by CIs with a narrower range (CI = 1.70 to 2.51 vs 1.88 to 3.04). The results achieved were not the same for safety, as MT showed neither effect on mortality at 90-days follow-up nor a statistically significant increase likelihood of SICH within seven days.
The various definitions of SICH combined with low event rates across the eight trials was proposed to confound the overall effect for the SICH outcome, thereby contributing to the uncertainty around the impact of MT on SICH. More data on mortality and SICH is needed and should be reported in ongoing trials.
The TSA confirmed that the meta-analyses fulfilled the information size requirement to satisfy the criterion for ‘sufficient evidence’ on the effectiveness and mortality, but not on increased risk of SICH. The authors conclude that no further trials to evaluate the effectiveness of MT versus no MT are warranted, in particular with stent retrievers and aspiration devices. Uncertainty remains as to whether MT reduces mortality or is associated with increased risk of SICH.
Given the robustness and generalizability of the evidence base for MT, there is a pressing need to invest in acute stroke care services to support delivery of this complex high technology service to all eligible patients.
The original article “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” is available in the Online First section of the European Stroke Journal.
1- Flynn D., Francis R., Halvorsrud K., et al 2017. 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. European Stroke Journal. 2017
2- Wetterslev J., Jakobsen JC., Gluud C. 2017. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Med Res Methodol. 2017 Mar 6; 17(1):39