Values of Baseline Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score for Treatment Decision of Acute Basilar Artery Occlusion
Abstract
Background and Purpose:
This study aimed to analyze the impact of baseline posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS) on the efficacy and safety of endovascular therapy (EVT) for patients with acute basilar artery occlusion.
Methods:
The BASILAR was a nationwide prospective registry of consecutive patients with a symptomatic and radiologically confirmed acute basilar artery occlusion within 24 hours of symptom onset. We estimated the effect of standard medical therapy alone (SMT group) versus SMT plus EVT (EVT group) for patients with documented pc-ASPECTS on noncontrast CT, both as a categorical (0–4 versus 5–7 versus 8–10) and as a continuous variable. The primary outcomes included favorable functional outcomes (modified Rankin Scale ≤3) at 90 days and mortality within 90 days.
Results:
In total, 823 cases were included: 468 with pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397), 317 with pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 38 with pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25). EVT was associated with higher rate of favorable outcomes (adjusted relative risk with 95% CI, 4.35 [1.30–14.48] and 3.20 [1.68–6.09]; respectively) and lower mortality (60.8% versus 77.6%, P=0.005 and 35.0% versus 66.2%, P<0.001; respectively) than SMT in the pc-ASPECTS 5 to 7 and 8 to 10 subgroups. Continuous benefit curves also showed the superior efficacy and safety of EVT over SMT in patients with pc-ASPECTS ≥5. Furthermore, the prognostic effect of onset to puncture time on favorable outcome with EVT was not significant after adjustment for pc-ASPECTS (adjusted odds ratio, 0.98 [95% CI, 0.94–1.02]).
Conclusions:
Patients of basilar artery occlusion with pc-ASPECTS ≥5 could benefit from EVT. The baseline pc-ASPECTS appears more important for decision making and predicting prognosis than time to EVT.
Registration:
URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1800014759.
Introduction
Acute basilar artery occlusion (BAO) carries a dismal outlook; in the absence of recanalization, nearly 80% of patients die or survive with severe disabilities.1 The efficacy of endovascular therapy (EVT) for BAO has been demonstrated in multiple observational studies,2–4 allowing a pooled 80% successful reperfusion.5 Recently, some prospective studies suggested that patients with acute BAO treated with EVT plus standard medical therapy (SMT) may experience better functional outcomes than those treated with SMT alone.6,7 Nevertheless, these studies did not establish imaging criteria to identify patients most likely to benefit from EVT. Appropriate patient selection based on baseline neuroimaging is important for EVT, and the criteria need to be further refined.
The posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS), first proposed by Puetz et al,8 is a semi-quantitative method for grading irreversible ischemia in the vertebrobasilar system. Previous studies have highlighted the importance of pc-ASPECTS on outcomes of BAO after EVT.9,10 A high pc-ASPECTS at baseline often implies higher rates of functional independence and lower mortality. However, whether baseline pc-ASPECTS modifies EVT effects in patients with BAO remains unclear. Several studies have shown that the pc-ASPECTS <8 could identify patients unlikely to achieve favorable outcomes despite recanalization of the basilar artery.8,11 However, more recent data demonstrated that a substantial number of patients with scores below this threshold may still do well after EVT if recanalization occurs rapidly.12 Thus, a lower threshold may be more appropriate for treatment selection.
The EVT for Acute Basilar Artery Occlusion study (BASILAR) reported the largest multicenter consecutive BAO cohort with a wide extent of baseline infarction. Therefore, we sought to examine the safety and efficacy of EVT compared with SMT for prespecified pc-ASPECTS strata (0–4 versus 5–7 versus 8–10). Furthermore, we aimed to characterize the variability of EVT treatment outcomes associated with baseline pc-ASPECTS and important time metrics.
Methods
The data that support the findings of this study are available from the corresponding author upon reasonable request.
The BASILAR Registry and Patient Selection
The BASILAR study enrolled patients with a symptomatic and radiologically confirmed acute BAO within 24 of symptom onset from 47 comprehensive stroke centers in china between January 2014 and May 2019.7 Patients were divided into 2 groups based on the initial treatment intent: either SMT alone (SMT group) or SMT plus EVT (EVT group). Further information on the inclusion and exclusion criteria and interventions can be found in information I in the Data Supplement. Patients who were evaluated early ischemic changes using pc-ASPECTS based on noncontrast CT (NCCT) images were included in this subgroup analysis. The ethics committees at participating centers have approved the study protocol. Besides, written informed consent was obtained from all patients or their legal representatives.
Variables and Imaging Analysis
The severity of stroke was assessed using the National Institutes of Health Stroke Scale (NIHSS) score at admission. Estimated time of BAO was defined as the time of symptom onset consistent with a clinical diagnosis of BAO; if the exact time was unknown, time of onset was recorded as the last well time by the witness.1
An independent core imaging laboratory, blinded to clinical outcomes and treatment assignment, evaluated all available imaging data. The pc-ASPECTS on baseline was graded according to the previous description.8 Each region was scored 0 if abnormal or 1 if normal; a higher pc-ASPECTS represents a smaller infarct. Each imaging scan was separately interpreted by 2 trained neuroradiologists (Drs Chen and Qiu). In cases of discrepancies, a third neuroradiologist (Dr Zi) confirmed the pc-ASPECTS. Collateral status was evaluated using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system.2,13 Reperfusion was assessed using the modified post-procedural Thrombolysis in Cerebral Infarction (mTICI) scale, ranging from mTICI 0 (no reperfusion) to 3 (complete reperfusion). Successful reperfusion was defined as a final mTICI score 2b to 3.
Study Outcomes
The primary efficacy outcome was favorable functional outcome defined as a modified Rankin Scale (mRS) score ≤3 at 90 days. The secondary clinical end points included shifts in scores over the entire range of mRS and functional independence (mRS score 0–2) at 90 days. Prespecified safety outcomes included all-cause mortality within 90 days and symptomatic intracerebral hemorrhage (SICH) within 48 hours, confirmed on CT scans or magnetic resonance imaging. Intracerebral hemorrhages were evaluated according to the Heidelberg Bleeding Classification.14 SICH was defined as an increased NIHSS score ≥4 or any parenchymal intracerebral hemorrhage. Besides, procedure-related complications (eg, arterial perforation, arterial dissection, and embolization) and serious adverse events were recorded and compared.
Statistical Analysis
Statistical analyses were performed using SPSS version 23 (IBM Corp., Armonk, NY) and STATA version 15.2 (StataCorp LLC, TX). A 2-tailed P<0.05 was considered statistically significant. Missing data for baseline characteristics and outcomes were imputed using multiple imputation, as detailed in Information I in the Data Supplement. Univariate comparisons were performed using Fisher exact test or χ2 test for categorical variables, Kruskal Wallis test or Mann–Whitney U test for continuous variables. Interobserver agreement for pc-ASPECTS assignment was evaluated using the weighted κ statistic.
The effects of EVT on binary outcomes in trichotomized pc-ASPECTS subgroups were assessed using Poisson regression model or binary logistic regression model, adjusting for age, sex, history of diabetes or ischemic stroke, baseline NIHSS, onset to imaging time, and location of occlusion. An ordinal regression model was performed to calculate the common odds ratio for a shift towards a 1-point improvement of mRS. We assessed heterogeneity of EVT treatment effect across trichotomized pc-ASPECTS subgroups by introducing an interaction term between treatment modality and trichotomized pc-ASPECTS (0–4 versus 5–7 versus 8–10) into the model. We also did sensitivity analyses using propensity score matching or the population based on the actual treatment received (Information I in the Data Supplement). Furthermore, comparisons for outcomes between treatments were performed using binary logistic regression model, with implementation of pc-ASPECTS as a continuous variable. To generate benefit curves related to the treatment modalities, outcome-specific predicted probabilities for continuous pc-ASPECTS values were computed with setting other variables in the model to mean values.
The second part only included patients in the EVT group. A multivariate logistic regression model was used to assess the variables independently associated with 90-day favorable outcomes, adjusting for any variables with P<0.10 in the univariate analysis. The association of onset to puncture time (OPT) or puncture-to-recanalization time with favorable outcomes were shown in adjusted margin plots. We also assessed the relationships of EVT outcomes with the continuous pc-ASPECTS and these time metrics. Distribution surfaces representing changes in predicted outcome probabilities were generated using SigmaPlot 12.5, with models assessed using the R2 correlation metric.
Results
Baseline Characteristics
Six patients were missing a pretreatment pc-ASPECTS in the BASILAR study and excluded from the current analysis. Finally, this subgroup analysis consisted of 823 patients, including 169 in the SMT group and 654 in the EVT group. The median (interquartile range) age, NIHSS score, and pc-ASPECTS for the cohort were 65 (57–74) years, 26 (16–33), and 8 (7–9), respectively. With a weighted κ value of 0.71 (95% CI, 0.68–0.75), the interobserver agreement for the grading of pc-ASPECTS on NCCT images was good.
Baseline characteristics for the trichotomized pc-ASPECTS subgroups and treatment modality are summarized in Table 1 and Table I in the Data Supplement. There were 38 of 823 patients who had pc-ASPECTS 0 to 4 (SMT: 13; EVT: 25), 317 had pc-ASPECTS 5 to 7 (SMT: 85; EVT: 232), and 468 had pc-ASPECTS 8 to 10 (SMT: 71; EVT: 397). Patients with lower pc-ASPECTS had higher NIHSS scores, worse collateral grades, longer median times from onset to puncture, and lower rates of successful recanalization (Table I in the Data Supplement).
| pc-ASPECTS 0–4 | pc-ASPECTS 5–7 | pc-ASPECTS 8–10 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| SMT (n=13) | EVT (n=25) | P value | SMT (n=85) | EVT (n=232) | P value | SMT (n=71) | EVT (n=397) | P value | |
| Age, y, median (IQR) | 63 (55–73) | 62 (55–69) | 0.794 | 65 (58–74) | 65 (58–74) | 0.258 | 67 (59–75) | 64 (56–73) | 0.032 |
| Women, n/total n (%) | 4 (30.8) | 8 (32.0) | 1.000* | 21 (24.7) | 67 (28.9) | 0.483 | 21 (29.6) | 95 (23.9) | 0.310 |
| Baseline NIHSS, median (IQR) | 36 (27–36) | 33 (30–35) | 0.177 | 24 (14–33) | 28 (18–33) | 0.140 | 26 (14–30) | 25 (15–32) | 0.276 |
| Premorbid mRS, n/total n (%) | 1.000* | 0.286 | 0.444* | ||||||
| 0 | 12 (92.3) | 22 (88.0) | 68 (80.0) | 201 (86.6) | 63 (88.7) | 328 (82.6) | |||
| 1 | 1 (7.7) | 3 (12.0) | 9 (10.6) | 19 (8.2) | 5 (7.0) | 50 (12.6) | |||
| 2 | 0 | 0 | 8 (9.4) | 12 (5.2) | 3 (4.2) | 19 (4.8) | |||
| History, n/total n (%) | |||||||||
| Ischemic stroke | 6 (46.2) | 7 (28.0) | 0.301* | 23 (27.1) | 53 (22.8) | 0.436 | 17 (23.9) | 80 (20.2) | 0.468 |
| Hypertension | 8 (61.5) | 18 (72.0) | 0.714* | 57 (67.1) | 168 (72.4) | 0.352 | 60 (84.5) | 271 (68.3) | 0.006 |
| Diabetes | 1 (7) | 7 (28.0) | 0.222* | 21 (24.7) | 63 (27.2) | 0.662 | 12 (16.9) | 83 (20.9) | 0.440 |
| Coronary heart disease | 4 (30.8) | 6 (24.0) | 0.709* | 12 (14.1) | 41 (17.7) | 0.452 | 9 (12.7) | 60 (15.1) | 0.594 |
| Atrial fibrillation | 1 (7.7) | 4 (16.0) | 0.643* | 12 (14.1) | 46 (19.8) | 0.244 | 9 (12.7) | 88 (22.2) | 0.069 |
| Intravenous thrombolysis, n/total n (%) | 1 (7.7) | 7 (28.0) | 0.222* | 17 (20.0) | 39 (16.8) | 0.509 | 22 (31.0) | 79 (19.9) | 0.036 |
| Location of occlusion, n/total n (%) | 0.057* | <0.001 | 0.001 | ||||||
| Distal BA | 2 (15.4) | 14 (56.0) | 18 (21.2) | 71 (30.6) | 18 (25.4) | 141 (35.5) | |||
| Middle BA | 7 (53.8) | 5 (20.0) | 50 (58.8) | 71 (30.6) | 39 (54.9) | 122 (30.7) | |||
| Proximal BA | 1 (7.7) | 2 (8.0) | 5 (5.9) | 47 (20.3) | 8 (11.3) | 58 (14.6) | |||
| VA–V4 | 3 (23.1) | 4 (16.0) | 12 (14.1) | 43 (18.5) | 6 (8.5) | 76 (19.1) | |||
| Time metrics, min, median (IQR) | |||||||||
| Onset-puncture time | NA | 436 (286–671) | NA | NA | 360 (233–518) | NA | NA | 310 (205–469) | NA |
| Onset-imaging time | 300 (45–501) | 252 (205–545) | 0.508 | 204 (70–365) | 233 (88–371) | 0.459 | 161 (88–368) | 183 (85–329) | 0.800 |
| Door-needle time | 82 (51–110) | 51 (40–68) | 0.272 | 71 (49–116) | 58 (50–93) | 0.723 | 59 (44–86) | 75 (50–107) | 0.183 |
| Puncture-recanalization time | NA | 104 (83–153) | NA | NA | 114 (77–163) | NA | NA | 100 (67–140) | NA |
| Stenting, n/total n (%) | 0 | 6 (24.0) | 0.076* | 0 | 81 (35.7) | <0.001 | 0 | 114 (29.5) | <0.001 |
| Collateral grade, n/total n (%) | 0.643* | 0.350 | 0.444 | ||||||
| ASITN/SIR grade 0–1 | 12 (92.3) | 20 (80.0) | 56 (65.9) | 166 (71.6) | 39 (54.9) | 210 (52.9) | |||
| ASITN/SIR grade 2 | 1 (7.7) | 5 (20.0) | 19 (22.4) | 50 (21.6) | 17 (23.9) | 121 (30.5) | |||
| ASITN/SIR grade 3–4 | 0 | 0 | 10 (11.8) | 16 (6.9) | 15 (21.1) | 66 (16.6) | |||
| mTICI score 2b/3, n/total n (%) | NA | 17 (68.0) | NA | NA | 176 (75.9) | NA | NA | 337 (84.9) | NA |
ASITN/SIR grade indicates the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral score; BA, basilar artery; EVT, endovascular treatment plus standard medical therapy; IQR, interquartile range; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction Score; NIHSS, National Institutes of Health Stroke Scale; pc-ASPECTS, posterior circulation Acute Stroke Prognosis Early Computed Tomography Score; SMT, standard medical therapy; and VA–V4, V4 of vertebral artery.
*
Fisher exact test.
Outcomes of EVT Versus SMT Stratified by pc-ASPECTS
Irrespective of treatment modality, only one (2.6%) patient with pc-ASPECTS 0 to 4 had an mRS ≤3 at 90 days. However, a favorable outcome was observed in 39 (12.3%) patients with pc-ASPECTS 5 to 7 and in 184 (39.3%) patients with pc-ASPECTS 8 to 10 (Table II in the Data Supplement). There were significantly better trends towards favorable outcome after EVT than SMT in patients with pc-ASPECTS 5 to 7 (15.5% versus 3.5%, P=0.004) and patients with pc-ASPECTS 8 to 10 (43.8% versus 14.1%, P<0.001, Table 2). Similarly, the rates of functional independence (mRS 0–2) were higher but mortality were lower in the EVT group compared with the SMT group in the 2 upper pc-ASPECTS sub-populations. The rates of SICH were numerically higher with EVT than SMT in the trichotomized pc-ASPECTS subgroups though only the difference in pc-ASPECTS 5 to 7 subgroup was statistically significant (7.3% versus 0.0%, P=0.022). Procedure-related complications and severe adverse events are also listed in Table 2 and Table II in the Data Supplement. In addition, results of these clinical outcomes were consistent after 1:1 propensity score matching analysis (Table III in the Data Supplement).
| pc-ASPECTS 0–4 | pc-ASPECTS 5–7 | pc-ASPECTS 8–10 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| SMT (n=13) | EVT (n=25) | P value | SMT (n=88) | EVT (n=229) | P value | SMT (n=78) | EVT (n=390) | P value | |
| Clinical outcomes, n/total n (%) | |||||||||
| mRS 0–2 | 0 | 1 (4.0) | 1.000* | 1 (1.2) | 26 (11.2) | 0.005 | 8 (11.3) | 154 (38.8) | <0.001 |
| mRS 0–3 | 0 | 1 (4.0) | 1.000* | 3 (3.5) | 36 (15.5) | 0.004 | 10 (14.1) | 174 (43.8) | <0.001 |
| Mortality | 11 (84.6) | 20 (80.0) | 1.000* | 66 (77.6) | 141 (60.8) | 0.005 | 47 (66.2) | 139 (35.0) | <0.001 |
| Any intracranial hemorrhage | 0 | 5 (20.0) | 0.144* | 0 | 21 (9.1) | 0.004 | 1 (1.4) | 40 (10.1) | 0.017 |
| SICH | 0 | 5 (20.0) | 0.144* | 0 | 17 (7.3) | 0.022 | 1 (1.4) | 26 (6.5) | 0.151 |
| Procedural-related complications, n/total n (%) | |||||||||
| Arterial perforation | NA | 0 | NA | NA | 2 (0.9) | NA | NA | 5 (1.3) | NA |
| Arterial dissection | NA | 0 | NA | NA | 4 (1.7) | NA | NA | 5 (1.3) | NA |
| Distal embolization | NA | 2 (8.3) | NA | NA | 10 (4.4) | NA | NA | 15 (3.8) | NA |
| Severe adverse events, n/total n (%) | |||||||||
| Pulmonary infection | 9 (69.2) | 22 (88.0) | 0.203* | 68 (80.0) | 179 (77.2) | 0.589 | 54 (76.1) | 289 (72.8) | 0.567 |
| Hemicraniectomy | 1 (7.7) | 0 | 0.342* | 1 (1.2) | 6 (2.6) | 0.745 | 0 | 8 (2.0) | 0.478 |
| Respiratory Failure | 7 (53.8) | 18 (72.0) | 0.301* | 38 (44.7) | 122 (52.6) | 0.214 | 26 (36.6) | 121 (30.5) | 0.305 |
| Circulatory failure | 6 (46.2) | 10 (40.0) | 0.742* | 22 (25.9) | 76 (32.8) | 0.241 | 17 (23.9) | 62 (15.6) | 0.085 |
| Ulcer | 1 (7.7) | 8 (32.0) | 0.126* | 16 (18.8) | 46 (19.8) | 0.842 | 18 (25.4) | 62 (15.6) | 0.045 |
| Venous thrombosis | 0 | 1 (4.0) | 1.000* | 3 (3.5) | 14 (6.0) | 0.551 | 2 (2.8) | 28 (7.1) | 0.281 |
EVT indicates endovascular treatment plus standard medical therapy; mRS, modified Rankin Scale; pc-ASPECTS, posterior circulation Acute Stroke Prognosis Early Computed Tomography Score; SICH, symptomatic intracranial hemorrhage; and SMT, standard medical therapy.
*
Fisher exact test.
Figure 1 illustrates the 90-day mRS distribution of both treatment allocations for pc-ASPECTS subgroups. In comparison with SMT, EVT was associated with higher rates of favorable outcomes (mRS 0–3) in the pc-ASPECTS 5 to 7 subgroup (adjusted relative risk [RR], 4.35 [95% CI, 1.30–14.48]) and pc-ASPECTS 8 to 10 subgroup (adjusted RR, 3.20 [95% CI, 1.68–6.09]; Table 3). The interaction between the effect of EVT treatment and the pc-ASPECTS subgroups was not significant (relative to pc-ASPECTS 8–10: pc-ASPECTS 5–7: adjusted RR, 1.45 [95% CI, 0.38–5.55]). A significant effect of EVT was still observed for the mortality, functional independence and shift in mRS analysis in the 2 upper pc-ASPECTS subgroups. In regard to SICH, there was only enough sample data to calculate a result for the pc-ASPECTS 8 to 10 subgroup, and the difference was not statistically significant between the EVT and SMT groups (adjusted RR, 4.09 [95% CI, 0.55–30.60]). Sensitivity analysis in the as-treated population also showed a significant improvement in these clinical outcomes favoring EVT over SMT in the pc-ASPECTS 5 to 7 and pc-ASPECTS 8 to 10 subgroups (Table IV in the Data Supplement).
| Effect variables | pc-ASPECTS 0–4 | pc-ASPECTS 5–7 | pc-ASPECTS 8–10 | P value for interaction 0–4 vs 8–10 | P value for interaction 5–7 vs 8–10 | ||||
|---|---|---|---|---|---|---|---|---|---|
| Adjusted effect (95% CI) | P value | Adjusted effect (95% CI) | P value | Adjusted effect (95% CI) | P value | ||||
| Primary outcomes | |||||||||
| mRS 0–3 | RR* | † | † | 4.35 (1.30–14.48) | 0.007 | 3.20 (1.68–6.09) | <0.001 | 0.987 | 0.586 |
| Mortality | OR‡ | 0.03 (0.00–76.80) | 0.390 | 0.36 (0.19–0.68) | 0.002 | 0.19 (0.10–0.36) | <0.001 | 0.228 | 0.292 |
| Secondary clinical outcomes | |||||||||
| mRS shift | Common OR§ | 3.66 (0.25–54.46) | 0.367 | 3.10 (1.66–5.79) | <0.001 | 5.19 (2.94–9.17) | <0.001 | 0.227 | 0.273 |
| mRS 0–2 | RR* | † | † | 9.54 (1.26–72.14) | 0.029 | 3.61 (1.76–7.39) | <0.001 | 0.989 | 0.322 |
| SICH | RR* | † | † | † | † | 4.09 (0.55–30.60) | 0.170 | 0.995 | 0.988 |
EVT indicates endovascular treatment plus standard medical therapy; mRS, modified Rankin Scale; OR, odds ratio; pc-ASPECTS, posterior circulation Acute Stroke Prognosis Early Computed Tomography Score; RR, relative risk; and SICH, symptomatic intracranial hemorrhage.
*
Relative risk of achievement of end points with EVT treatment.
†
Not enough data available to calculate statistical parameter.
‡
Odds of death with EVT treatment.
§
Odds of improved functional outcome (ie, shift to lower mRS) with EVT treatment.
Outcomes of EVT Versus SMT Associated With Numeric pc-ASPECTS
Figure 2A illustrates the predicted probabilities of favorable outcome of both treatment modalities with pc-ASPECTS increment as a continuous variable. The odds of favorable outcome increased by 96% in the SMT group (adjusted OR, 1.96 [95% CI, 1.22–3.14]) and by 70% in the EVT group (adjusted OR, 1.70 [95% CI, 1.48–1.95]) for each pc-ASPECTS growth. There was no interaction modulating treatment effects between the EVT and the SMT groups (P=0.407), with the former being consistently better than the latter; an obvious difference was observed when the pc-ASPECTS was ≥5.
The odds of mortality significantly declined by 22% in the SMT group (adjusted OR, 0.78 [95% CI, 0.62–0.99]) and by 26% in the EVT group (adjusted OR, 0.74 [95% CI, 0.67–0.82]) with each pc-ASPECTS increment change. Similarly, the EVT group had a substantially lower probability of death within 90 days than the SMT group when the pc-ASPECTS was ≥5 (Figure 2B).
Outcomes of EVT Associated With Numeric pc-ASPECTS and Time
Restricting the analysis to just the EVT group, the univariate results and logistic regression analyses are presented in Table V in the Data Supplement. The patients with favorable outcomes had shorter OPTs (303 [202–433] versus 340 [234–504], P=0.014) and procedure time (85 [60–128] versus 113 [79–158], P<0.001) than those with unfavorable outcomes.
A continuous time-effect predicted probability curve, demonstrating the relationship between OPT and favorable outcomes, is shown in Figure 3A. Favorable outcome rates numerically declined as the OPT increased. However, OPT was not associated with a favorable outcome at 90 days after adjusting for confounding factors. On the contrary, we observed a significant detrimental effect of extended procedure time on favorable outcomes (Figure 3B), with a decline of 6% risk for each 10 minutes extension (adjusted OR, 0.94 [95% CI, 0.90–0.97]).
Figure 3C and 3D illustrates the effects of pc-ASPECTS and time metrics on the probability of favorable outcome with EVT. There was no interaction on favorable outcomes between the pc-ASPECTS and OPT (P=0.354).The effect of longer OPT on favorable outcomes was similar to the effect of shorter OPT in a specified baseline pc-ASPECTS (adjusted OR, 0.98 [95% CI, 0.94–1.02], P=0.339 for OPT). The interaction between the pc-ASPECTS and procedure time was also not significant (P=0.463). However, the effect of procedure time on prognostic outcomes was not consistent among patients with different pc-ASPECTS scores, with a steeper time-benefit slope in patients with higher pc-ASPECTS.
Discussion
This study evaluated, for the first time, the efficacy and safety of EVT compared with SMT in patients with acute BAO presenting with different pc-ASPECTS scores. Although the treatment effect of EVT was not modified by the trichotomized pc-ASPECTS, the benefit/risk ratio of EVT substantially varied among the 3 subgroups. The pc-ASPECTS strata seemed to be a useful tool for selecting patients for an emergent recanalization procedure. In addition, our data showed evidence that in a specified pc-ASPECTS, the efficacy of EVT for BAO was independent of time from onset to puncture but significantly associated with the time from puncture to recanalization.
The baseline pc-ASPECTS was a strong prognostic variable, and patients with higher pc-ASPECTS fared better, consistent with previous studies.11,12 Our study further provided novel information regarding the benefit curves for EVT versus SMT with changes of pc-ASPECTS; we showed that the efficacy and safety of EVT was superior to SMT alone in BAO patients, especially in those with pc-ASPECTS ≥5. Meanwhile, EVT carried no substantially increased risk of procedure-related complications and adverse events, as indicated by our results and others’.15 An SICH was observed in 17 (7.3%) patients with pc-ASPECTS 5-7 after EVT, obviously higher than the 0% observed after SMT. However, compared with the pooled 6.8% (95% CI, 3.5%–10.8%) in a meta-analysis5 and the 8% reported in the BEST trial6 for the entire EVT cohort, the rate of SICH seen in this subgroup is considered acceptable. Taken together, the benefit-to-risk ratio of EVT is higher than that of SMT for patients with acute BAO with pc-ASPECTS ≥5.
Treating physicians often face greater uncertainty when deciding whether to proceed with EVT in patients with pc-ASPECTS 5 to 7 due to limited available evidence. Some studies indicated that baseline pc-ASPECTS <8 was not associated with beneficial outcomes following EVT8,11; however, recent evidence showed patients with extensive ischemic damage could still benefit from rapid recanalization.12 A good outcome (mRS 0–2) was reported in 11(24.4%) and mortality occurred only in 10 (22%) of patients with BAO with DWI-pc-ASPECTS ≤6 after EVT.16 These findings, however, were limited by the small sample size and lack of a control group. In our subpopulation, the overall proportion of favorable outcomes associated with EVT was limited to 15% and mortality reached up to 61%. One possible explanation could be that our patients in this subgroup had more severe stroke deficits with 72.1% having an NIHSS ≥20 and a lower proportion achieving mTICI 2b/3 (75.5%), both of which are well-known factors for worse prognosis.4,17 Nevertheless, compared with the 96.5% rate of severe disability or death in conservatively managed patients with BAO with pc-APSECTS 5 to 7, that was also reported in previous studies,10,11 an absolute increment of 10% in favorable outcomes and reduction of 17% in mortality after EVT was still encouraging. Further randomized data are warranted to substantiate the efficacy of EVT among patients with pc-ASPECTS 5 to 7.
In contrast, patients with pc-ASPECTS 0 to 4 had a markedly poor outcome irrespective of treatment modality. Overall, only 2.6% of these patients achieved favorable outcomes and 81.6% were deceased by 3 months. Although the outcome-modifying effect of EVT among pc-ASPECTS subgroups was not significant, this finding might be underpowered due to small numbers in this subgroup. Coupled with multiple subgroups and unequal subgroup sizes, the false-negative risk is particularly high.18 Indeed, the 4.0% difference in favorable outcome supporting the EVT represented a difference of only one patient. Besides, the incidences of SICH and some adverse events were more common in patients undergoing EVT than SMT, though the difference was not significant due to small sample sizes. Therefore, the absolute benefit of EVT in these patients seems to be marginal relative to the overall risk and poor prognosis.
Another important finding was that the favorable outcome probabilities with EVT appeared to be stable across OPTs, even up to 24 hours after onset, in a specified baseline pc-ASPECTS. This suggests that pc-ASPECTS was a more critical factor influencing benefit from EVT over time, supporting a tissue-based patient selection strategy as large-vessel occlusion in anterior circulation.19,20 Evidence showed that, in patients who have survived hours after symptom onset, there may be a robust collateral arterial network maintaining brittle patency of brain stem perforators, which may improve treatment benefits from delayed recanalization.21,22 Consistent with our results, a previous study demonstrated a similar functional outcome after recanalization between those with short onset to treatment time and longer time categories.4,10 However, this does not mean that there is no need to receive treatment as soon as possible because each patient likely has a unique optimal time window for therapy due to inherent variability in collateral support. Moreover, patients with lower pc-ASPECTS often had much longer times from symptom onset to puncture, as indicated by our results and others’,9 providing evidence that the chance of a favorable pc-ASPECTS will probably decrease with time delay, resulting in deleterious effects.
The effect of procedure time on EVT outcomes was described recently, showing extended procedures not only decreased functional independence but also increased incidence of complications, possibly due to difficult vascular situations and multiple attempts to achieve a good mTICI score.23,24 Our findings reinforce the notion that prolonged procedures could have a negative effect on a patient’s outcomes. There was a 6% lower risk of achieving unassisted ambulation for every 10 minutes extension. However, we failed to provide a procedure timeframe as studies proposed to abort failed thrombectomies, with target time<60 minutes.24,25 Of note, patients with high pc-ASPECTS tolerated longer procedure times in our study, implying that a terminal time selection might vary with baseline ischemic damage. Moreover, procedure time was associated with multiple additional factors, including stroke type, occlusion site, vascular status, interventionalist experience26 as well as thrombectomy device.27 It seems difficult to define an optimal timeframe regarding these complex clinical associations based on these nonrandomized data; therefore, it might be more appropriate to evaluate each operation on its own merits.
This study had several limitations. While this was a prospective cohort, the effect of EVT or SMT on clinical outcomes was determined in a nonrandomized fashion. Hence, the study holds all the drawbacks of an observational design. Second, the results of pc-ASPECTS 0 to 4 subgroup should be interpreted with caution due to the small number of patients. However, because there was no explicit imaging exclusion criterion based on the extent of pretreatment ischemic injuries in the BASILAR registry, our study population with pc-ASPECTS 0 to 4 was the largest among recent researches of EVT. Third, NCCT could not be as accurate as advanced imaging modalities (eg, magnetic resonance imaging and CT perfusion) in determining the baseline infarct size. However, NCCT is an inexpensive, fast, and routine first-line modality. Besides, the advanced imaging was reported to result in a 57-minute delay in decision making, without substantial benefits in patient outcomes.28 Understanding the instructional and prognostic value of NCCT findings is of practical importance for EVT. Additionally, a pc-ASPECTS does not reflect the critical location or volume of the lesion. Thus, deviation from predicted outcomes is not uncommon even in patients with same pc-ASPECTS.
Conclusions
In conclusion, patients with baseline pc-ASPECTS ≥5 could profit from EVT treatment after BAO, even when treatment is delayed after onset. Furthermore, the extent of ischemic changes (pc-ASPECTS) upon presentation appears to be more important than the time from onset to treatment in predicting the benefits of EVT. Besides, extended procedure times reduce the probability of favorable outcomes among EVT-treated patients. Strategies to reduce the duration of procedure may herald an opportunity to improve patient outcomes.
Acknowledgments
We thank all the coinvestigators of BASILAR (The EVT for Acute Basilar Artery Occlusion Study) for their dedication to the study.
Footnote
Nonstandard Abbreviations and Acronyms
- BAO
- basilar artery occlusion
- EVT
- endovascular therapy
- mRS
- modified Rankin Scale
- mTICI
- modified Thrombolysis in Cerebral Infarction Score
- NCCT
- noncontrast computed tomography
- NIHSS
- National Institutes of Health Stroke Scale
- OPT
- onset to puncture time
- OR
- odds ratio
- pc-ASPECTS
- posterior circulation Acute Stroke Prognosis Early Computed Tomography Score
- SICH
- symptomatic intracranial hemorrhage
- SMT
- standard medical therapy
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© 2021 American Heart Association, Inc.
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History
Received: 17 June 2020
Revision received: 5 November 2020
Accepted: 11 December 2020
Published online: 11 February 2021
Published in print: March 2021
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Disclosures None.
Sources of Funding
This work was supported by the Youth Program of National Natural Science Foundation of China (No. 81801157), National Science Fund for Excellent Young Scholars (No. 81822015), National Science Fund for Distinguished Young Scholars (No. 81525008), and the Army Medical University Clinical Medical Research Talent Training Program (No. 2019XLC2008 and No. 2019XLC3016).
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