Control-matched octo/nonagenarian outcomes in acute basilar artery occlusions treated with mechanical thrombectomy—analysis of the PC-SEARCH thrombectomy registry

Abstract

Introduction

Age is often used as a predictor in determining outcomes in large vessel occlusions treated with mechanical thrombectomy. However, limited data exist for octo/nonagenarian outcomes compared to younger individuals in acute basilar artery occlusions treated with thrombectomy.

Methods

Patient data were obtained from the PC-SEARCH Thrombectomy Registry which consists of 444 acute basilar artery occlusions treated with mechanical thrombectomy. Individuals were dichotomized based on age (>80 and ≤80 years old). Primary outcome was defined as modified Rankin Scale of 0–3 at 90 days. Logistic and multivariate regression, as well as control-matched analysis, were performed.

Results

There were 373 and 71 patients in the younger and older cohorts, respectively. Gender, ethnicity, smoking status, atrial fibrillation, and coronary artery disease were noted to be significantly different between cohorts. At 90 days, 178 (47.7%) and 23 (32.4%) patients achieved primary outcome at 90 days (p = 0.02), however, after controlling for potentially confounding factors this association lost significance (OR 0.50 95% CI 0.24–1.05; p = 0.07). There were 84 patients included in the control matched analysis and demonstrated no significant differences on multivariate analysis between cohorts (OR 0.68 95% CI 0.25–1.84; p = 0.45).

Interpretation

Octa/nonagenarians presenting with an acute basilar artery occlusion treated with mechanical thrombectomy can achieve acceptable rates of favorable functional outcomes compared to younger individuals with similar baseline demographic and stroke characteristics.

Introduction

Octo/nonagenarians are underrepresented in mechanical thrombectomy studies for large vessel occlusion ischemic strokes, and, subsequently, data remain scarce.^1–5 In an increasingly aging population, this highlights an important area of interest. While the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke Trials (HERMES) and other observational studies demonstrate thrombectomy benefit in the anterior circulation, with the differences in morbidity and mortality of posterior circulation, this population needs to be evaluated.^1,6 Furthermore, differing rates of complications among the elderly population have been observed and further investigations would help clinicians anticipate postprocedural requirements. ¹ For instance, the Acute Basilar Artery Occlusion Study (BASILAR) demonstrated worsened outcomes in patients greater than 75 years old compared to a younger cohort; albeit still improved compared to medical management. ⁷

In the Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion (BAOCHE) and Endovascular treatment for Acute Basilar Artery Occlusion: A multicenter randomized controlled trial (ATTENTION), this trend continued to be observed.^4,5 Yet, with the primary goal of demonstrating thrombectomy benefit in basilar artery occlusions in these studies, there remains a peri- and postprocedural knowledge gap in the elderly population. In this study, we aimed to evaluate octo/nonagenarians and compared them to a younger cohort to evaluate favorable functional outcomes at 90 days. Since there is some evidence to suggest that both the elderly and posterior circulation ischemic stroke have a higher tendency to have hemorrhagic conversion, we additionally investigated rates of symptomatic intracranial hemorrhage (sICH).^6,8–10

Methods

Study design and participants

We performed a comparative cohort study using data from The Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-Procedural Predictors for Mechanical Thrombectomy (PC-SEARCH Thrombectomy). PC-SEARCH is a multicenter retrospective collaboration from eight high-volume centers in the United States consisting of consecutive patients with basilar artery occlusions treated with mechanical thrombectomy between January 2015 and December 2021. Inclusion criteria were age of 18 years or greater, presence of acute BAO on admission CTA, MRA or/and Digital Subtraction Angiography, and use of mechanical thrombectomy. This study was approved under a waiver of informed consent by the local institutional review boards at each participating center and is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. ¹¹ Patients included in this collaboration are not exclusively enrolled in this registry and may have been included in other registries or meta-analysis. ¹²

Data for the registry were compiled from respective participating sites per the proposal supplied by the hosting institution and each site was responsible for obtaining local IRB approval. The hosting site did not receive data sheets with identifying information and did not require consent from patients as no information was required beyond the de-identified data. Data will be made available by request to the corresponding author.

Study groups and data elements

Patients were divided into two groups based on age: (1) >80 years of age and (2) ≤80 years of age. Preprocedural data including last known well, presenting National Institute of Health Stroke Scale (NIHSS), the Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTs), intravenous tPA administration, door-to-tPA time, and clot location were compiled. Intraprocedural details included time-of-puncture, puncture-first pass, puncture-to-reperfusion time, intra-arterial tPA administration, Thrombolysis in Cerebral Infarction (TICI) score, first-pass recanalization defined as achieving TICI score ≥2b in a single pass without further attempts, and total number of passes. Patient outcome data included 90-day mRS and Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) sICH. ¹³

Primary and secondary outcomes

The primary outcome for the study was favorable functional outcome at 90 days, measured as a mRS score of 0–3, obtained by board certified vascular neurologists during a routinely scheduled clinical visit or by a certified nurse during a standardized telephone interview at each center. This outcome was defined to be consistent with existing literature.^4,5 Secondary outcomes included functional independence, measured as mRS 0–2, at 90 days. The primary safety outcome was sICH, as defined according to the SITS-MOST criteria. ¹³

Statistical analysis

Parametric and nonparametric descriptive statistics were analyzed using mean, median, percentage totals, standard deviation, and interquartile ranges as appropriate. A univariate analysis was performed for clinical characteristics and outcomes. Comparison of parametric continuous variables was analyzed by Student t-test, and nonparametric variables were analyzed with Mann–Whitney U test. Statistics for categorical variables were compared with a chi-squared analysis. Scale variables were correlated with outcomes and dependent variables correlated with outcome measures with more than two categories were compared using analysis of variance.

Functional outcome measures were dichotomized into favorable (mRS ≤ 3) and unfavorable (mRS > 3). Adjusted odds ratios were performed on dependent variables with respect to preprocedural characteristics reaching p values less than 0.20.

Case–control analysis was performed. Patients were matched on gender, ethnicity, presenting NIHSS, and pc-ASPECTS variables. Baseline and stroke characteristics were compared as described in the primary analysis. Unadjusted and adjusted analyses were additionally performed on the matched patients with respect to preprocedural characteristics reaching p values less than 0.20. Statistical significance was defined as two-tailed and reaching a p value less than 0.05. Analysis was performed using IBM SPSS statistics package 28.

Results

General cohort

There were 444 patients included in the general analysis. There were 373 and 71 patients ≤80 and >80 cohorts. Patients in the >80 cohort were less likely to be male (44% vs. 59%, p = 0.04), current smokers (14% vs. 36%, p < 0.01) but more likely to be white (63% vs. 55%, p = 0.01) and demonstrated higher rates of atrial fibrillation (49% vs. 20%, p < 0.01) compared to the ≤80 cohort (Table 1).

Table 1.

Demographics.

	Primary Analysis (N = 444)			Case–Control Matching (N = 84)
	AGE ≤ 80 (N = 373)	AGE > 80 (N = 71)	p value	AGE ≤ 80 (N = 42)	AGE > 80 (N = 42)	p value
Age (mean, SD)	61 (13)	86 (4)	<0.01	63 (13)	86 (4)	<0.001
Gender, male (N, %)	219 (59%)	31 (44%)	0.04	23 (55%)	23 (55%)	1.00
Ethnicity (N, %)
White	205 (55%)	45 (63%)	0.01	35 (83%)	35 (83%)	1.00
Black	55 (15%)	3 (4%)		3 (7%)	3 (7%)
Asian	2 (<1%)	1 (1%)		0 (0%)	0 (0%)
Other	13 (3.5%)	7 (10%)		4 (9%)	4 (10%)
Hypertension (N, %)	257 (69%)	53 (75%)	0.33	30 (71%)	31 (74%)	0.81
History of stroke (N, %)	70 (19%)	9 (13%)	0.21	8 (19%)	4 (10%)	0.20
Smoking (N, %)	134 (36%)	10 (14%)	<0.01	13 (31%)	7 (17%)	0.11
Atrial fibrillation (N, %)	73 (20%)	35 (49%)	<0.01	10 (24%)	21 (50%)	0.01
Diabetes mellitus (N, %)	119 (32%)	15 (21%)	0.07	13 (31%)	9 (21%)	0.32
Coronary artery disease (N, %)	78 (21%)	25 (35%)	<0.01	12 (29%)	12 (29%)	1.00
Intracranial atherosclerosis (N, %)	110 (29%)	20 (28%)	0.63	18 (43%)	14 (33%)	0.37
Hyperlipidemia (N, %)	170 (46%)	33 (46%)	0.89	26 (62%)	19 (45%)	0.13
Premorbid mRS (median, IQR)	0 (0–1)	0 (0–1)	0.071	0 (0–1)	0 (0–1)	0.80

Presenting stroke and time metrics were similar between each cohort. There was a trend toward more distal clot location in the >80 cohort (41% vs. 28% p = 0.1) (Table 2).

Table 2.

Stroke characteristics.

	AGE ≤ 80 (N = 373)	AGE > 80 (N = 71)	p value	AGE ≤ 80 (N = 42)	AGE > 80 (N = 42)	p value
Initial NIHSS	17 (9–25)	16 (9–25)	0.69	17 (9–25)	16 (9–25)	0.74
NIHSS Groups
NIHSS ≤ 10	117 (31%)	19 (27%)	0.55	13 (31%)	13 (31%)	1.00
NIHSS 11–20	94 (25%)	22 (31%)		13 (31%)	13 (31%)
NIHSS > 20	156 (42%)	29 (41%)		16 (38%)	16 (38%)
pc-ASPECTS
<10	133 (36%)	24 (34%)	0.77	18 (43%)	18 (43%)	1.00
=10	240 (64%)	47 (66%)		24 (57%)	24 (57%)
Location
Proximal	121 (32%)	17 (24%)	0.1	18 (43%)	14 (33%)	0.37
Middle	54 (14%)	9 (13%)		8 (19%)	7 (17%)
Distal	104 (28%)	29 (41%)		13 (31%)	20 (48%)
Last known well, mins (median, IQR)	198 (60–602)	217 (36–623)	0.99	409 (115–660)	176 (34–595)	0.12
IV-TPA (N, %)	85 (23%)	14 (20%)	0.43	11 (26%)	10 (24%)	0.80
Door-to-tPA, mins (median, IQR)	64 (43–103)	40 (20–66)	0.13	82 (38–125)	40 (20–66)	0.51
Door-to-puncture, mins (median, IQR)	86 (48–149)	73 (29–109)	0.62	101 (62–157)	73 (26–109)	0.19
TICI ≥ 2b (N, %)	236 (63%)	46 (65%)	0.86	34 (81%)	33 (79%)	0.59
IA-tPA (N, %)	18 (5%)	5 (7%)	0.49	4 (10%)	4 (10%)	1.00

There were 201 patients achieving favorable functional outcomes at 90 days. In the >80 cohort, there were 23 (32.4%) patients achieving favorable functional outcomes compared 178 (47.7%) patients in the ≤80 cohort (p = 0.02). On multivariate analysis controlling for potential confounding factors, significance was not retained (OR 0.50, 95% CI 0.24–1.05; p = 0.07). Secondary outcomes for mRS 0–2 demonstrated equivalent outcomes (OR 0.56, 95% CI 0.26–1.22; p = 0.15) on multivariate analysis. Odds of sICH were similar between cohorts (OR 1.51, 95% CI 0.46–5.03; p = 0.50) (Table 3 and Figure 1).

Table 3.

Primary, secondary, and safety outcomes.

	All Patients				Case Control Matched Population
	Unadjusted		Adjusted a		Unadjusted		Adjusted b
	OR (95% CI)	p value	OR (95% CI)	p value	OR (95% CI)	p value	OR (95% CI)	p value
mRS 0–3	0.53 (0.31–0.90)	0.02	0.50 (0.24–1.05)	0.07	0.60 (0.24–1.46)	0.26	0.68 (0.25–1.84)	0.45
mRS 0–2	0.47 (0.26–0.87)	0.02	0.56 (0.26–1.22)	0.15	0.79 (0.31–2.05)	0.63	1.05 (0.35–3.08)	0.94
sICH	1.29 (0.46–3.60)	0.63	1.51 (0.46–5.03)	0.50	2.71 (0.49–14.84)	0.25	5.44 (0.48–62.02)	0.17

^aAdjusted for baseline characteristics reaching p < 0.2 including gender, ethnicity, smoking status, atrial fibrillation, diabetes mellitus, coronary artery disease, and premorbid mRS.

^bAdjusted for baseline characteristics reaching < 0.2 including history of stroke, smoking status, atrial fibrillation, and hyperlipidemia.

Figure 1.

Patient flow chart.

Case–control matched cohort

There were 84 patients included in the controlled analysis with 42 patients in each cohort. There were no significant baseline differences in demographic or stroke characteristics between each cohort (Tables 1 and 2).

There were 31 patients who achieved favorable functional outcomes at 90 days with 13 (31%) and 18 (43%) patients in the >80 and ≤80 cohorts, respectively (p = 0.26). Multivariate analysis controlling for potentially confounding factors (OR 0.68, 95% CI 0.25–1.84; p = 0.45) demonstrated comparable benefit to the younger cohort. Odds of achieving functional independence was equivalent between cohorts (OR 1.05, 95% CI 0.35–3.08; p = 0.94). There was a trend toward higher rates of sICH in the >80 cohort (12% vs. 5%; p = 0.24). These results are paralleled in the multivariate analysis (OR 5.44, 95% CI 0.48–62.02; p = 0.17).

Discussion

In this study, we evaluated the outcomes of acute basilar artery occlusion treated with mechanical thrombectomy in an elderly cohort. Functional outcomes and sICH data collected from the PC-SEARCH Thrombectomy Registry analyzed octo/nonagenarian and younger cohorts. We demonstrated that there were no significant differences on multivariate analysis. We attempted to limit selection bias by further case–control matched analysis and additionally demonstrated equivalent outcomes.

Prior studies have demonstrated heterogenous acute basilar artery thrombectomy outcomes in the elderly population.^3–5 For instance, the Basilar Artery International Cooperation Study (BASICS) demonstrated higher rates of poor functional outcome at one month (defined as mRS 4–6) in the elderly population. ³ Yet, in this study, we demonstrated similar outcomes by three months. The contents of these studies highlight important counseling points. One, that expected outcomes in the elderly are delayed compared to a younger cohort and, two, that thrombectomy should not be withheld if an elderly patient is otherwise an appropriate candidate. This second point is also demonstrated in the BASILAR and ATTENTION study which revealed that older patients had better functional outcomes with mechanical thrombectomy compared to medical management. ¹⁴ Our study revealed that 32% of the elderly cohort treated with thrombectomy achieved favorable functional outcomes while ATTENTION had approximately 25% favorable functional outcome in patients who received medical management alone.

Generally, age has been inversely associated with functional outcomes in ischemic strokes. There are many factors playing toward this correlation. First, aging is related to increased morbidities that increase the risk of poor functional outcome and mortality. These comorbidities often preclude the elderly population to withstand the intense therapies offered at acute rehabilitation facilities and therefore subacute facilities are employed.^3,15,16 Second, neuronal plasticity decreases as one ages and accounts for the observed delayed recovery. As such, standard time frames of recovery are inappropriately applied to the elderly population and rehabilitation efforts are often terminated prior to obtaining full benefit. Third, although collateral circulation develops as vascular bed resistance increases, Arsava et al. demonstrated that collateral circulation decreases with age since neovascularization lacks the same vessel wall integrity.^17–19 With this in mind, timely reperfusion is further stressed in the elderly.

Symptomatic intracerebral hemorrhage is a known complication from stroke intervention. Our study demonstrated a nonsignificant trend toward higher rates of sICH in the elderly population (OR 5.44, 95% CI 0.48–62.02). In the ATTENTION and Multicenter Clinical Registry of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) registry, there was higher risk of sICH in those who received mechanical thrombectomy for basilar and anterior circulation occlusions.^5,10 A recent meta-analysis in 2023 of trials for basilar artery occlusion thrombectomy versus medical management alone, agreed that there is an increased risk of sICH in the mechanical thrombectomy group compared to the medical management group. ²⁰ ATTENTION did not show differences in sICH in different age groups, but this study had strict exclusion criteria for the included patients over 80 years old. ⁵ In contrast, this risk was not increased in the aging population compared to the younger cohort in ATTENTION, BASICS, and BASILAR studies.^3,16 When specifically evaluating sICH after mechanical thrombectomy in the elderly population, Bai et al. performed a meta-analysis that illustrated similar rates of sICH compared to the younger population in HERMES, near 4%. ¹ The trials included in the meta-analysis did not account for location of vessel occlusion.

This study has several limitations. First, the retrospective nature of the study predisposes our analysis to selection bias. We attempted to limit the selection bias using statistical methods; however, this cannot be overcome with the current study design. Second, this study lacked central radiographic adjudication and controlling for the baseline pc-ASPECTS in the case–control analysis may have limited this comparison. We simplified matching criteria to patients with and without hypodensity on initial CT scans. Third, our case–control analysis was a predominantly white population, and we cannot extrapolate these findings to other ethnicities with certainty.

Conclusion

Octa/nonagenarians presenting with an acute basilar artery occlusion treated with mechanical thrombectomy have similar safety and efficacy compared younger individuals with similar baseline demographic and stroke characteristics. Further studies are needed to improve patient selection in this population.