Author + information
- Jetan H. Badhiwala, MD,
- Branavan Manoranjan, BHSc and
- Saleh A. Almenawer, MD∗ ()
- ↵∗Division of Neurosurgery, Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4L8, Canada
The meta-analysis by Elgendy et al. (1) on mechanical thrombectomy for acute ischemic stroke pools estimates from 9 randomized trials. According to the study’s selection criteria, only trials that randomized patients within 4.5 h of stroke onset were included. However, strict application of this criterion should have resulted in exclusion of the MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy), MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), and ESCAPE (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke) trials. The authors’ rationale presumably was to evaluate a homogeneous population of patients who would have received intravenous tissue plasminogen activator (tPA) as their primary objective was to compare mechanical thrombectomy plus standard care (i.e., intravenous tPA) to standard care alone. Despite this, the use of intravenous tPA in the intervention group varied from 44% to 100%. Similarly, the authors excluded the SYNTHESIS (Local Versus Systemic Thrombolysis for Acute Ischemic Stroke) trial, because the thrombectomy group did not receive tPA. Nonetheless, when the SYNTHESIS trial was designed, the notion that mechanical thrombectomy and intravenous tPA could work synergistically was an unproven assumption, and there was concern about risk of hemorrhage. With the available published reports, it would have been most informative to perform an overall pooled analysis of mechanical thrombectomy (with/without intravenous tPA), and a subsequent sensitivity analysis stratified by concurrent use of intravenous tPA. In fact, a general shortcoming of the current study is the failure to investigate heterogeneity in the primary outcome (I2 = 54%), for example, through sensitivity/subgroup analyses of key variables that could impact the efficacy of thrombectomy. Heterogeneity in meta-analysis should be expected, but appropriately explained and quantified (2).
The authors included the THERAPY (Assess the Penumbra System in the Treatment of Acute Stroke) and THRACE (Trial and Cost Effectiveness Evaluation of Intra-Arterial Thrombectomy in Acute Ischemic Stroke) trials. However, both studies have yet to be published, and only intermediary results with incomplete follow-up are available from the THRACE trial. We recommend excluding these trials to limit risk of bias. In addition, the authors pool estimates from 9 trials, but do not examine the body of evidence using proper methodologies such as GRADE (Grading of Recommendations Assessment, Development and Evaluation). The PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) Statement (3) and Cochrane Collaboration (4) recommend to evaluate the confidence in cumulative evidence when conducting a meta-analysis to inform health practitioners with the strength of the examined evidence.
Using the GRADE methodology, our recent meta-analysis published in the Journal of the American Medical Association (5) demonstrated the safety and efficacy of endovascular therapy in improving revascularization and functional outcomes. We conducted subgroup/sensitivity analyses to explain the detected heterogeneity and variability of eligible studies. We found the relative benefit associated with endovascular intervention to be increased when combined with intravenous tPA, with confirmed proximal arterial occlusion on angiographic imaging, and with use of stent retrievers for mechanical thrombectomy.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Elgendy I.Y.,
- Kumbhani D.J.,
- Mahmoud A.,
- Bhatt D.L.,
- Bavry A.A.
- Higgins J.P.
- Shamseer L.,
- Moher D.,
- Clarke M.,
- et al.
- ↵Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [March 2011]. The Cochrane Collaboration; 2011.