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Abstract

Background and Purpose:

Endovascular thrombectomy (EVT) as an effective treatment acute ischemic stroke (AIS) due to large vessel occlusion of the anterior circulation (AC-LVO). Randomized trials of posterior circulation large vessel occlusion (PC-LVO) patients have failed to show a benefit of EVT over medical therapy (MT). We performed a systematic review and meta-analysis using the Nested Knowledge AutoLit living review platform to understand better whether EVT is beneficial for PC-LVO.

Methods:

On the AutoLit platform, we identified randomized control trials and prospective studies that reported functional outcomes in patients with PC-LVO treated with EVT versus MT. The primary outcome variable was 90-day modified Rankin Scale (mRS) 0-3, and secondary outcome variables included 90-day mRS 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). The Mantel-Haenzel method was used to calculate 95% confidence intervals (CIs) around the pooled effect sizes, and a separate random effects model was fit for each outcome measure.

Results

Three studies with 1,248 patients, 860 in the EVT arm and 388 in the MT arm, were included in the meta-analysis. The favorable outcome rate (mRS 0-3) in EVT patients was 39.9% (95% CI: 30.6-50.1%) versus 24.5% in MT patients (95% CI: 9.6-49.8%). EVT patients had higher mRS 0-2 rates (31.8% [95% CI: 25.7-38.5%] versus 19.7% [95% CI: 7.4-42.7%]) and lower mortality (42.1% [95% CI: 35.9-48.6%] versus 52.8% [95% CI: 33.3-71.5%]) compared to MT patients, but neither result was statistically significant. EVT patients were more likely to develop sICH (OR=10.36; 95% CI: 3.92-27.40).

Conclusions:

EVT treatment of PC-LVO trended toward superior functional outcomes and reduced mortality compared to MT despite a trend toward increased sICH in EVT patients. Existing randomized and prospective studies are insufficiently powered to demonstrate a benefit of EVT over MT in posterior circulation AIS patients.

Sunburst Diagram of Interventions and Outcomes
Sunburst Diagram of Interventions and OutcomesThe above figure displays the hierarchy of interventions and outcomes used in treating basilar artery LVO.

Results

Literature Search Results and Risk of Bias Assessment

Our initial search identified 237 studies, with 2 additional records identified through expert recommendation (Figure 3). After removing duplicates, a total of 226 articles were screened for inclusion. A total of 223 articles were excluded after screening based on title and abstract. A total of 3 full-text articles were assessed for eligibility and included in the final quantitative meta-analysis.9-11

Our risk of bias assessment identified 1 RCT of high quality (1++),10 1 RCT of moderate quality (1+),9 and 1 non-randomized study of high quality (2++).11 The results of our quality appraisal are summarized in Supplementary Table I.

Study-Specific Patient Demographics and Outcomes

From the three studies identified in our systematic review, a total of 1,248 patients were available for analysis. 388 (31.1%) patients were treated with MT alone and 860 (68.9%) patients were treated with EVT. Patient characteristics by study are presented in Table 1, and study-specific patient outcomes are provided in Table 2.

Qualitative appraisal of data

Qualitatively, both RCTs9, 10 showed that EVT compared to MT alone failed to demonstrate a significant difference in sICH, 90-day functional outcome, or mortality at 90 days. Conversely, the findings from Zi et al.11 suggested that EVT was associated with better functional outcomes and reduced mortality rate at 90 days; however, sICH was significantly higher with EVT compared to MT alone. Due to the considerable differences in findings between the RCTs and the non-randomized study, we performed additional sensitivity analyses restricting to only the higher quality RCTs9, 10 for each separate random-effects model, which are presented in turn below.

Primary Outcome: 90-day modified Rankin Score 0 - 3

The overall rate of 90-day mRS 0-3 for the EVT group was 39.9% (95% CI: 30.6-50.1), and for the MT group was 24.5% (95% CI: 9.6-49.8). There was no statistically significant difference in the odds of mRS 0-3 between the EVT and the MT group (OR=2.17; 95% CI: 0.41-11.52; p=0.185; Figure 4a). The estimated between-study variability in effect estimates unrelated to sampling error ranged from moderate to high (I2=84.3% [95% CI: 53.2%; 94.8%]).

TitleFirst AuthorYearInterventionArm SizemRs 0-3 (n/N)TICI 2b/3 (n/N)Mortality (n/N)sICH (n/N)
Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion.Langezaal, Lucianne C M2021Standard medical therapy only14655 / 146 (37.7%)63 / 146 (43.2%)1 / 146 (0.7%)
Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion.Langezaal, Lucianne C M2021Endovascular therapy plus/minus medical therapy15468 / 154 (44.2%)63 / 88 (71.6%)59 / 154 (38.3%)7 / 154 (4.5%)
Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.Liu, Xinfeng2020Standard medical therapy only6521 / 65 (32.3%)9 / 14 (64.3%)25 / 65 (38.5%)0 / 65 (0.0%)
Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.Liu, Xinfeng2020Endovascular therapy plus/minus medical therapy6628 / 66 (42.4%)45 / 63 (71.4%)22 / 66 (33.3%)5 / 66 (7.6%)
Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery OcclusionStandard medical therapy only10726 / 107 (24.3%)45 / 107 (42.1%)1 / 88 (1.1%)
Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery OcclusionEndovascular therapy plus/minus medical therapy11051 / 110 (46.4%)89 / 101 (88.1%)34 / 110 (30.9%)6 / 102 (5.9%)
Trial of Endovascular Treatment of Acute Basilar-Artery OcclusionStandard medical therapy only11426 / 114 (22.8%)63 / 114 (55.3%)0 / 114 (0.0%)
Trial of Endovascular Treatment of Acute Basilar-Artery OcclusionEndovascular therapy plus/minus medical therapy226104 / 226 (46.0%)208 / 223 (93.3%)83 / 226 (36.7%)12 / 226 (5.3%)

Discussion

In recent years, the success of EVT for the treatment of AC-LVO stroke has led to better functional outcomes for patients, especially those presenting outside of the traditional 3 – 4.5-hour window for intravenous thrombolysis.1-8 As neurointerventional technique and device development continues, focus must simultaneously be placed on determining the applicability of successful procedures to patient cohorts with inconclusive treatment decision algorithms. Patients presenting with PC-LVO strokes make up one such cohort, and this meta-analysis was designed on the novel Nested Knowledge AutoLit platform to study the effectiveness of EVT compared to MT alone in this cohort.

Numerous retrospective and single arm studies have found EVT to be effective for PC-LVO stroke treatment, but a lack of evidence from published prospective and RCTs remains to prove EVT efficacy in this population.19-23 We evaluated and pooled three studies that allow this comparison, with a separate sensitivity analysis to study the two RCTs alone given the discordant interpretation of the prospective cohort study data.9-11 Our results failed to show a convincing benefit for EVT compared to MT for PC-LVO stroke treatment, but there are several explanations for our unexpected findings. In both the global meta-analyses and the RCT-restricted analyses, the differences in rates of 90-day mRS 0-3 or 90-day functional independence between the EVT and the MT group were not significant. However, the magnitude and directionality of these differences must be noted. In the RCT-restricted analysis, the EVT group had a 90-day mRS 0-3 rate of 45.1% compared to 36.9% for the MT group. Similarly, the 90-day functional independence (mRS 0-2) rate in the EVT group was 31.8% compared to 19.7% for the MT group. Future RCTs on this topic may add sufficient power to this analysis to produce significant and clinically relevant findings for patients presenting with PC stroke.

References
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