Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Abstract

Importance: Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke.

Objective: To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke.

Data sources: MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015.

Study selection: Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected.

Data extraction and synthesis: Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes.

Main outcomes and measures: The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage.

Results: Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration.

Conclusions and relevance: This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment.

Fig 1. Flow selection of randomized controlled trials included in the meta-analysis.

Fig 2. Pooled effect estimates by restricted maximum likelihood random effects model with inverse variance weighting.

(A) Primary outcome of a shift in scores on modified Rankin Scale at 90 days between endovascular and medical management (common odds ratio, indicating odds of a more favorable distribution of scores on the modified Rankin Scale). (B) Secondary outcome of all-cause mortality (odds ratios). (C) Secondary outcome of symptomatic intra-cerebral hemorrhage (odds ratios).

Fig 3. Meta-regression analysis relating trial effect estimates to workflow efficiencies.

Mixed effects restricted maximum likelihood meta-regression models of log common odds ratios for improved functional outcome regressed against (A) median time from stroke onset to groin puncture and (B) median time from stroke onset to reperfusion, indicating that improved workflow efficiencies significantly influence the beneficial effects of endovascular treatment (P = 0.0077 and 0.0089, respectively).

Fig 4. Forest plots of meta-analyses for pooled odds ratios and risk ratios for functional independence (modified Rankin Scale scores of 0 to 2).

Patients randomized to endovascular intervention with retrievable stents have (A) 2.47 (95% CI: 1.92 to 3.18) times greater odds and (B) 1.69 (95% CI: 1.46 to 1.95) times greater probability of experiencing functional independence at 90-days post-stroke compared to those randomized to medical management.

Fig 5. Influence analyses for pooled effects on primary and secondary outcomes.

Removal of any single trial does not significantly influence the pooled effect of endovascular therapy on (A) the primary outcome of a beneficial shift in mRS score distributions, (B) the secondary outcome of mortality or (C) the secondary outcome of symptomatic intra-cerebral hemorrhage.