Elsevier

The Lancet Neurology

Volume 19, Issue 2, February 2020, Pages 115-122
The Lancet Neurology

Articles
Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial

https://doi.org/10.1016/S1474-4422(19)30395-3Get rights and content

Summary

Background

Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion.

Methods

We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556.

Findings

Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0–3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81–3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0–3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20–7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31–7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group.

Interpretation

There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study.

Funding

Jiangsu Provincial Special Program of Medical Science.

Introduction

Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating acute ischaemic stroke due to large vessel occlusion.1, 2, 3, 4 However, these trials were limited to occlusive lesions involving the proximal anterior circulation. Whether endovascular treatment is beneficial for acute vertebrobasilar artery occlusion remains unknown. Although basilar occlusion accounts for approximately 1% of all ischaemic strokes and 5–10% of all proximal intracranial occlusions, it represents a neurological catastrophe, with severe disability and death occurring in about 70% of patients.5, 6 Available studies on endovascular treatment of acute vertebrobasilar artery occlusion are limited by small sample size, uncontrolled data, and heterogeneous and obsolete treatment approaches.5, 7, 8, 9

Research in context

Evidence before the study

We searched PubMed with no language restrictions for papers published from Jan 1, 2010, to June 30, 2019, using the search terms “endovascular therapy”, “intra-arterial treatment”, or “mechanical thrombectomy” crossed with “basilar artery occlusion” or “vertebrobasilar artery occlusion”, and “randomized controlled trial”. We identified only one previous randomised trial for vertebrobasilar occlusion. However, this trial used an obsolete treatment method (urokinase infusion) and ended prematurely because of poor recruitment, with only 16 participants. A few non-randomised prospective studies of intra-arterial treatment for vertebrobasilar occlusion have been reported. Although some of these studies have included controls, they had many methodological limitations and were unable to provide any definite evidence regarding the specific benefit of endovascular therapy for patients with acute vertebrobasilar occlusions. We did not find any randomised controlled trials of modern thrombectomy devices for the treatment of acute vertebrobasilar occlusion.

Added value of this study

To our knowledge, our study is the first randomised controlled trial to assess the effect of contemporary endovascular therapy, including stent-retriever-based mechanical thrombectomy, in the treatment of acute vertebrobasilar occlusion. The early termination of the study due to drop in valid recruitment and high crossover rate is consistent with the expected loss of equipoise in face of the several trials showing an overwhelming benefit of thrombectomy in anterior circulation strokes, as well as the known poor outcomes of patients with untreated vertebrobasilar occlusions with severe presentation. Despite not meeting its prespecified primary endpoint on intention-to-treat analysis, the secondary prespecified per-protocol and as-treated analyses of our trial provided some evidence to show that patients undergoing endovascular therapy might have better outcomes than those managed with standard medical treatment alone.

Implications of all the available evidence

The overall evidence points to a benefit of endovascular reperfusion of large vessel occlusion strokes. Our data confirm the poor outcomes of untreated patients presenting with acute vertebrobasilar occlusion and severe clinical findings, and support the overall safety and potential efficacy of early endovascular treatment in this patient population. As seen in our trial, equipoise in this context has been lost in most clinical settings where mechanical thrombectomy can be safely done.

In the Basilar Artery Occlusion Endovascular Intervention versus Standard Medical Treatment (BEST) trial, we aimed to compare endovascular treatment plus standard medical therapy with standard medical therapy alone for the treatment of patients with acute ischaemic stroke due to vertebrobasilar occlusion within 8 h of estimated occlusion time.

Section snippets

Study design and participants

The BEST trial was a multicentre, prospective, open-label, randomised controlled trial with blinded assessment of endpoints, done at 28 stroke centres in China. The trial protocol was approved by the institutional review board of each participating site. The trial was designed and conducted by a steering committee, which was composed of independent academic investigators and statisticians. The trial protocol and statistical analysis plan are available in the appendix (pp 1–111).

Patients were

Results

Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for trial eligibility. Of these, 131 (45%) were enrolled and randomly assigned to the intervention group (66 patients) or control group (65 patients; figure 1). The study was terminated prematurely by the steering committee according to the recommendation of the data and safety monitoring board because of excessive crossovers and progressive drop in the average rate of valid per-centre recruitment (appendix pp 120–21). In the

Discussion

On the basis of its prespecified intention-to-treat analysis, the BEST trial did not show a benefit of mechanical thrombectomy over standard medical therapy alone for the treatment of basilar artery occlusion within 8 h of estimated occlusion time. However, our results might have been confounded by the fact that equipoise was lost over the course of the study, as shown by the high crossover rates and progressive drop in the average rate of valid per-centre recruitment, which eventually led to

Data sharing

The study protocol, statistical analysis plan, and de-identified participant data that underlie the results of this Article will be available for investigators after approval of a study proposal by a review committee within the next 12 months. Please email the corresponding authors for more information.

References (22)

  • X Liu et al.

    Acute basilar artery occlusion: Endovascular Interventions versus Standard Medical Treatment (BEST) Trial-Design and protocol for a randomized, controlled, multicenter study

    Int J Stroke

    (2017)
  • Cited by (0)

    *

    Contributed equally

    BEST Trial Investigators listed in the appendix

    View full text