Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysisBMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i1754 (Published 18 April 2016) Cite this as: BMJ 2016;353:i1754
- Filipe Brogueira Rodrigues, specialty trainee and researcher1 2 3,
- Joana Briosa Neves, specialty trainee3,
- Daniel Caldeira, specialty trainee and researcher1 2,
- José M Ferro, professor of neurology4,
- Joaquim J Ferreira, professor of neurology and pharmacology1 2 4,
- João Costa, professor of pharmacology1 2 5 6
- 1Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Av Prof Egas Moniz 1649-035, Lisbon, Portugal
- 2Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal
- 3Department of Medicine, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Portugal
- 4Department of Neurosciences, Neurology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Portugal
- 5Center for Evidence-Based Medicine, Faculty of Medicine, University of Lisbon, Portugal
- 6Portuguese Collaborating Center of the IberoAmerican Cochrane Network, Faculty of Medicine, University of Lisbon, Portugal
- Correspondence to: F B Rodrigues
Objectives To evaluate the efficacy and safety of endovascular treatment, particularly adjunctive intra-arterial mechanical thrombectomy, in patients with ischaemic stroke.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, SciELO, LILACS, and clinical trial registries from inception to December 2015. Reference lists were crosschecked.
Eligibility criteria for selecting studies Randomised controlled trials in adults aged 18 or more with ischaemic stroke comparing endovascular treatment, including thrombectomy, with medical care alone, including intravenous recombinant tissue plasminogen activator (rt-PA). Trial endpoints were functional outcome (modified Rankin scale scores of ≤2) and mortality at 90 days after onset of symptoms. No language or time restrictions applied.
Results 10 randomised controlled trials (n=2925) were included. In pooled analysis endovascular treatment, including thrombectomy, was associated with a higher proportion of patients experiencing good (modified Rankin scale scores ≤2) and excellent (scores ≤1) outcomes 90 days after stroke, without differences in mortality or rates for symptomatic intracranial haemorrhage, compared with patients randomised to medical care alone, including intravenous rt-PA. Heterogeneity was high among studies. The more recent studies (seven randomised controlled trials, published or presented in 2015) proved better suited to evaluate the effect of adjunctive intra-arterial mechanical thrombectomy on its index disease owing to more accurate patient selection, intravenous rt-PA being administered at a higher rate and earlier, and the use of more efficient thrombectomy devices. In most of these studies, more than 86% of the patients were treated with stent retrievers, and rates of recanalisation were higher (>58%) than previously reported. Subgroup analysis of these seven studies yielded a risk ratio of 1.56 (95% confidence interval 1.38 to 1.75) for good functional outcomes and 0.86 (0.69 to 1.06) for mortality, without heterogeneity among the results of the studies. All trials were open label. Risk of bias was moderate across studies. The full results of two trials are yet to be published.
Conclusions Moderate to high quality evidence suggests that compared with medical care alone in a selected group of patients endovascular thrombectomy as add-on to intravenous thrombolysis performed within six to eight hours after large vessel ischaemic stroke in the anterior circulation provides beneficial functional outcomes, without increased detrimental effects.
Systematic review registration PROSPERO CRD42015019340.
Contributors: JJF and JC are the guarantors. All authors except for JMF contributed to the drafting of the manuscript, the development of the selection criteria, the risk of bias assessment strategy, and data extraction criteria. FBR developed the search strategy. FBR and JBN conducted the report screening, study inclusion, data extraction, and result interpretation and discussion. DC performed the statistical analysis and intrepted and discussed the results. JMF, JJF, and JC provided expertise on stroke. JJF and JC also provided expertise on methods. All authors read, provided feedback, and approved the final manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: This study received no funding.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: no author has support for the submitted work; JJF has speaker and consultant relationships with GlaxoSmithKline, Novartis, TEVA, Lundbeck, Solvay, Abbott, Bial, Merck-Serono, Grunenthal, and Merck Sharp and Dohme that might have an interest in the submitted work in the previous three years; their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and FBR, JBN, DC, and JC have no non-financial interests that may be relevant to the submitted work. JMF received in the past three years speaker fees from Boehringer Ingelheim and consultancy fees from Boehringer Ingelheim, Lundbeck, and Daichi Sankyo.
Ethical approval: Not required.
Data sharing: No additional data available.
Transparency: The lead authors (JC and JJF) affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.