Key Points
Question
Is age associated with functional outcomes and mortality among patients with large ischemic stroke undergoing endovascular thrombectomy?
Findings
In this cohort study including 408 patients who received endovascular thrombectomy for large ischemic strokes, older age was associated with worse functional outcomes. However, older age did not significantly modify the clinical benefit of successful mechanical reperfusion in acute ischemic stroke with large infarct.
Meaning
This age-based analysis of functional outcomes could assist clinicians in decision-making for older patients with large ischemic stroke receiving endovascular thrombectomy.
This cohort study evaluates whether age is associated with functional outcomes and mortality among patients with acute ischemic strokes with large infarct who undergo endovascular thrombectomy.
Abstract
Importance
Randomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials.
Objective
To provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct.
Design, Setting, and Participants
This retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes.
Exposure
Age.
Main Outcomes and Measures
Primary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6).
Results
A total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27).
Conclusions and Relevance
In this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.
Introduction
Acute ischemic stroke is a leading cause of disability and death worldwide.1 The incidence of acute ischemic stroke increases steeply with older age. With rapidly aging populations in Europe, North America, and parts of Asia, the absolute number of patients with acute ischemic stroke will inevitably increase over the next decades.2,3
Large vessel occlusions represent a subgroup of acute ischemic stroke with particularly poor clinical prognosis. Since the pivotal thrombectomy trials in 2015, endovascular thrombectomy has become standard of care in addition to best medical treatment in patients with acute ischemic stroke due to large vessel occlusion.4,5,6 Although these trials were not specifically designed to investigate the treatment effect in older patients, results from the HERMES meta-analysis7 and the DAWN trial8 provide strong evidence that endovascular thrombectomy reduces long-term disability also in patients aged 80 years and older. Accordingly, current guidelines refuse an upper age limit and recommend mechanical thrombectomy in selected patients aged 80 years and older.9
Recent randomized clinical trials demonstrated efficacy and safety of endovascular thrombectomy in selected patients with acute ischemic stroke and already established large infarct, commonly defined as an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 0 to 5.10,11,12,13 Importantly, patients older than 80 years were underrepresented, selected more stringently, or even fully excluded from these trials. Thus, data on endovascular thrombectomy in older patients with established large infarct remain scarce, although this subgroup is frequently encountered in acute stroke management and will gain more importance in health care systems with aging populations. We performed an age-based analysis of functional outcomes in a clinical dataset to support prognosis and informed decision-making in endovascular thrombectomy for acute ischemic stroke with large infarct.
Methods
Study Design
We conducted a retrospective multicenter cohort study of patients who were enrolled in the German Stroke Registry–Endovascular Treatment (GSR-ET) between May 1, 2015, and December 31, 2021. The GSR-ET is an ongoing, open-label, industry-independent, prospective, multicenter registry enrolling patients with acute ischemic stroke due to large vessel occlusion who received endovascular thrombectomy in 1 of 25 comprehensive stroke centers in Germany (ClinicalTrials.gov identifier: NCT03356392).14,15 The GSR-ET was approved by the ethics committee of the Ludwig Maximilian University, Munich, Germany. The local ethics committee of each participating center gave approval to contribute fully anonymized data to the GSR-ET. Thus, informed consent was waived after ethics committee review. The study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.16
Study Cohort
The following inclusion criteria were defined: (1) age of 18 years or older; (2) prestroke modified Rankin Scale (mRS) score of 0 to 3; (3) acute ischemic stroke in the anterior circulation; (4) isolated proximal large vessel occlusion of the intracranial internal carotid artery or of the M1 segment of the middle cerebral artery; (5) established large infarct defined as an ASPECTS of 0 to 5 on pretreatment noncontrast computed tomography (CT) or magnetic resonance imaging (MRI); (6) treatment with endovascular thrombectomy; and (7) available information about the admission National Institutes of Health Stroke Scale (NIHSS) score, the final modified Thrombolysis In Cerebral Infarction (mTICI) grade, and the 90-day mRS score. The following exclusion criteria were defined: (1) occlusion of the extracranial internal carotid artery including tandem occlusions and (2) concomitant stenting therapy. A flowchart of the inclusion and exclusion criteria is provided in eFigure 1 in Supplement 1.
Clinical and Radiological Assessment
Baseline, imaging, treatment, and outcome characteristics were extracted from the GSR-ET database. Imaging characteristics were used as reported by the local investigators at each participating center. A final mTICI grade of 2b or 3 was considered successful reperfusion, and a final mTICI grade of 0, 1, or 2a was considered unsuccessful reperfusion. In accordance with Second European Cooperative Acute Stroke Study (ECASS II), symptomatic intracranial hemorrhage (sICH) was defined as the presence of any intracranial hemorrhage on follow-up imaging within 24 hours and a neurological worsening of 4 or more points on the NIHSS.17 Clinical assessments were performed at baseline, at 24 hours, and at 90 days using the NIHSS and mRS.
Outcome Measures
The primary outcomes were the rate of independent ambulation at 90 days and mortality censored at 90 days. Independent ambulation was defined as an mRS score of 0 to 3 and mortality as an mRS score of 6.
Statistical Analysis
Descriptive statistics were used to compare characteristics (1) between patients aged 60 years and younger, 61 to 70 years, 71 to 80 years, and older than 80 years and (2) between patients aged 80 years and younger and older than 80 years (eFigure 2 in Supplement 1). The age thresholds were explicitly chosen to obtain a subgroup of patients older than 80 years, who were underrepresented in randomized clinical trials.7,12,18 Categorical variables were reported as counts and percentages. Continuous variables were reported as medians and IQRs. Statistical tests between subgroups were conducted using Pearson χ2 tests for categorical variables and nonparametrical Kruskal-Wallis 1-way analysis of variance tests for continuous variables.
Unadjusted and adjusted odds ratios (aORs) were estimated for binary outcome measures by binary logistic regression. Unadjusted and adjusted common odds ratios were estimated for ordinal outcome measures by ordinal logistic regression. Common odds ratios greater than 1 indicate a shift in the distribution of 90-day mRS scores toward better functional outcomes (ie, lower mRS scores). Odds ratios were reported with 95% CIs. Covariates were selected based on prior knowledge. Odds ratios were adjusted for sex, prestroke mRS, admission NIHSS, baseline ASPECTS, treatment with intravenous thrombolysis, final mTICI grade, and time between symptom onset or last known well to end of procedure.
Significant covariates from the regression models in eTable 1 in Supplement 1 were used to estimate predicted probabilities of independent ambulation at 90 days and death within 90 days stratified by age, prestroke mRS, admission NIHSS, and final mTICI grade. Interaction terms and predicted probabilities were calculated from the regression models in eTable 3 in Supplement 1 to investigate the association between age and clinical benefit of successful reperfusion compared with unsuccessful reperfusion.
We performed complete-case analysis for all regression models. A 2-tailed P < .05 was considered significant for all statistical tests. No adjustments were made for multiple comparisons. Analyses were conducted using R version 4.1.2 (R Project for Statistical Computing) and RStudio version 2023.03.0 + 386 (Rstudio).
Results
Patient Characteristics
Of 13 082 patients enrolled in the GSR-ET, 408 patients received endovascular thrombectomy for acute ischemic stroke with large infarct and met all further inclusion criteria (217 women [53.2%]; median [IQR] age, 75 [64-83] years) (Table 1; eFigure 2 in Supplement 1). Most patients had no disability or no significant disability before admission, indicated by a median (IQR) prestroke mRS of 0 (0-1). On admission to hospital, neurological impairment was generally severe, with a median (IQR) NIHSS score of 17 (14-20) points. The median (IQR) baseline ASPECTS was 5 (4-5). The intracranial internal carotid artery was occluded in 169 patients (41.4%) and the M1 segment of the middle cerebral artery in 239 (58.6%). Intravenous thrombolysis was administered in 1 of 3 patients (144 of 407 [35.4%]). A final mTICI grade of 2b or 3 was achieved in 334 of 408 patients (81.9%). The overall rate of sICH within 24 hours after endovascular thrombectomy was 7.0% (28 of 400 patients). Independent ambulation at 90 days, defined as an mRS score of 0 to 3, was observed in 118 patients (28.9%) and death within 90 days in 182 patients (44.6%).
Table 1. Baseline, Imaging, Treatment, and Outcome Characteristics, Stratified by Age in Endovascular Thrombectomy for Acute Ischemic Stroke With ASPECTS of 0 to 5.
| Characteristic | Patients, No./total No. (%) | |||||
|---|---|---|---|---|---|---|
| All patients (N = 408) | ≤60 y (n = 78) | 61-70 y (n = 85) | 71-80 y (n = 119) | >80 y (n = 126) | P valuea | |
| Baseline characteristics | ||||||
| Age, median (IQR), y | 75 (64-83) | 52 (47-57) | 67 (63-69) | 76 (74-78) | 86 (83-89) | NA |
| Sex | ||||||
| Male | 191/408 (46.8) | 53/78 (67.9) | 52/85 (61.2) | 45/119 (37.8) | 41/126 (32.5) | <.001b |
| Female | 217/408 (53.2) | 25/78 (32.1) | 33/85 (38.8) | 74/119 (62.2) | 85/126 (67.5) | |
| Arterial hypertension | 294/405 (72.6) | 33/78 (42.3) | 60/84 (71.4) | 96/118 (81.4) | 105/125 (84.0) | <.001b |
| Atrial fibrillation | 177/405 (43.7) | 9/78 (11.5) | 29/84 (34.5) | 62/118 (52.5) | 77/125 (61.6) | <.001b |
| Diabetes | 85/405 (21.0) | 9/78 (11.5) | 18/84 (21.4) | 27/118 (22.9) | 31/125 (24.8) | .14b |
| Dyslipidemia | 142/403 (35.2) | 15/78 (19.2) | 35/83 (42.2) | 45/117 (38.5) | 47/125 (37.6) | .01b |
| Prestroke mRS score, median (IQR) | 0 (0-1) | 0 (0-0) | 0 (0-0) | 0 (0-2) | 0 (0-1) | <.001c |
| Admission NIHSS score, median (IQR) | 17 (14-20) | 16 (12-19) | 17 (14-20) | 17 (15-21) | 18 (15-21) | .008c |
| Imaging characteristics | ||||||
| Pretreatment imaging | ||||||
| CT | 363/408 (89.0) | 61/78 (78.2) | 75/85 (88.2) | 107/119 (89.9) | 120/126 (95.2) | .002b |
| MRI | 54/408 (13.2) | 21/78 (26.9) | 10/85 (11.8) | 12/119 (10.1) | 11/126 (8.7) | .001b |
| Baseline ASPECTS, median (IQR) | 5 (4-5) | 4 (3-5) | 5 (4-5) | 5 (4-5) | 5 (4-5) | .07c |
| Occlusion site | ||||||
| Intracranial ICA | 169/408 (41.4) | 33/78 (42.3) | 36/85 (42.4) | 51/119 (42.9) | 49/126 (38.9) | .92b |
| MCA–M1 segment | 239/408 (58.6) | 45/78 (57.7) | 49/85 (57.6) | 68/119 (57.1) | 77/126 (61.1) | |
| Left occlusion side | 190/408 (46.6) | 34/78 (43.6) | 35/85 (41.2) | 55/119 (46.2) | 66/126 (52.4) | .39b |
| Workflow times | ||||||
| Symptom onset or LKW to admission, median (IQR), min | 220 (114-523) | 240 (107-505) | 195 (100-443) | 220 (120-593) | 246 (127-559) | .64c |
| Missing, No. | 37 | 11 | 6 | 10 | 10 | |
| Procedure time, median (IQR), min | 38 (25-62) | 39 (25-61) | 35 (23-52) | 36 (27-65) | 38 (24-64) | .49c |
| Missing, No. | 47 | 7 | 10 | 14 | 16 | |
| Treatment characteristics | ||||||
| Administration of IVT | 144/407 (35.4) | 25/78 (32.1) | 29/85 (34.1) | 47/119 (39.5) | 43/125 (34.4) | .71b |
| General anesthesia | 305/405 (75.3) | 62/77 (80.5) | 65/85 (76.5) | 87/118 (73.7) | 91/125 (72.8) | .62b |
| Recanalization attempts, median (IQR) | 2 (1-3) | 2 (1-4) | 2 (1-3) | 2 (1-3) | 2 (1-3) | .25c |
| mTICI grade 2b or 3 | 334/408 (81.9) | 65/78 (83.3) | 67/85 (78.8) | 98/119 (82.4) | 104/126 (82.5) | .62b |
| Outcome measures | ||||||
| 24h NIHSS score, median (IQR) | 17 (12-24) | 15 (7-26) | 17 (11-23) | 17 (14-24) | 18 (12-23) | .35c |
| Missing, No. | 38 | 2 | 13 | 12 | 11 | |
| sICH within 24 h | 28/400 (7.0) | 5/78 (6.4) | 10/83 (12.0) | 8/115 (7.0) | 5/124 (4.0) | .12b |
| 90-d mRS score, median (IQR) | 5 (3-6) | 3 (2-4) | 4 (3-6) | 6 (4-6) | 6 (5-6) | <.001c |
| Independent ambulation (90-d mRS score 0-3) | 118/408 (28.9) | 44/78 (56.4) | 31/85 (36.5) | 24/119 (20.2) | 19/126 (15.1) | <.001b |
| Death within 90 d (90-d mRS score 6) | 182/408 (44.6) | 12/78 (15.4) | 27/85 (31.8) | 62/119 (52.1) | 81/126 (64.3) | <.001b |
Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomography Score; CT, computed tomography; ICA, internal carotid artery; IVT, intravenous thrombolysis; LKW, last known well; MCA, middle cerebral artery; MRI, magnetic resonance imaging; mRS, modified Rankin Scale; mTICI, modified Thrombolysis in Cerebral Infarction; NA, not applicable; NIHSS, National Institutes of Health Stroke Scale; sICH, symptomatic intracranial hemorrhage.
Characteristics were compared between subgroups with the use of either Kruskal-Wallis test for continuous variables or Pearson χ2 test for categorical variables.
Pearson χ2 test.
Kruskal-Wallis test.
Patient Characteristics Stratified by Age
The study cohort was subdivided into the age groups of 60 years and younger, 61 to 70 years, 71 to 80 years, and older than 80 years (Table 1). A total of 78 patients (19.1%) with acute ischemic stroke and large infarct were aged 60 years and younger; 85 (20.8%) aged 61 to 70 years; 119 (29.2%) aged 71 to 80 years; and 126 (30.9%) older than 80 years. The rates of comorbidities, prestroke mRS, and admission NIHSS increased significantly in older age groups. MRI was used in patients aged 60 years and younger more than 3 times as often as in patients older than 80 years (21 patients [26.9%] vs 11 patients [8.7%]; P = .001). Workflow times and treatment characteristics, including intravenous thrombolysis, general anesthesia, and final mTICI grade of 2b or 3, did not differ between age groups. The percentage of patients with independent ambulation at 90 days was 56.4% in those aged 60 years and younger (44 patients) and decreased gradually to 15.1% in those older than 80 years (19 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001) (Figure 1).
Figure 1. Distribution of Scores on the Modified Rankin Scale (mRS), Independent Ambulation, and Mortality at 90 Days, Stratified by Age in Patients With Acute Ischemic Stroke and Large Infarct.
A, The dashed line marks mRS score of 6 (death), and the solid line marks mRS scores of 0, indicating no symptoms; 1, no clinically significant disability; 2, slight disability; and 3, moderate disability (the patient can walk unassisted). mRS score of 4 indicates moderately severe disability and 5, severe disability.
Comparison Between Patients Aged 80 Years and Younger and Those Older Than 80 Years
The study cohort was dichotomized to compare functional and safety outcomes between patients aged 80 years and younger and those older than 80 years (Table 2). The median (IQR) 90-day mRS score was 4 (3-6) in patients aged 80 years and younger and 6 (5-6) in patients older than 80 years (P < .001). There was a shift in the distribution of 90-day mRS scores toward worse functional outcomes in patients older than 80 years compared with patients aged 80 years and younger (adjusted common OR, 0.38; 95% CI, 0.23-0.62; P < .001).
Table 2. Comparison of Outcome Measures Between Patients Aged 80 Years and Younger and Those Older Than 80 Years in Endovascular Thrombectomy for Acute Ischemic Stroke With ASPECTS of 0 to 5.
| Outcome | Patients, No./total No. (%) | P valuea | Unadjusted OR (95% CI)b | P value | Adjusted OR (95% CI)c | P value | |
|---|---|---|---|---|---|---|---|
| ≤80 y (n = 282) | >80 y (n = 126) | ||||||
| Functional outcomes | |||||||
| Independent ambulation (90-d mRS score 0-3) | 99/282 (35.1) | 19/126 (15.1) | <.001d | 0.33 (0.19-0.56) | <.001 | 0.44 (0.23-0.82) | .01 |
| Death (90-d mRS score 6) | 101/282 (35.8) | 81/126 (64.3) | <.001d | 3.23 (2.09-5.23) | <.001 | 2.75 (1.61-4.72) | <.001 |
| 90-d mRS score, median (IQR) | 4 (3-6) | 6 (5-6) | <.001e | 0.31 (0.20-0.47)f | <.001 | 0.38(0.23-0.62)f | <.001 |
| Safety outcomes | |||||||
| sICH within 24 h | 23/276 (8.3) | 5/124 (4.0) | .12d | 0.46 (0.15-1.15) | .13 | NAg | NAg |
Abbreviations: ASPECTS, Alberta Stroke Program Early Computed Tomography Score; mRS, modified Rankin Scale; OR, odds ratio; sICH, symptomatic intracranial hemorrhage.
Characteristics were compared between patients aged 80 years and younger and those older than 80 years with the use of either Mann-Whitney U test for continuous variables or a χ2 test for categorical variables.
Univariable regression analysis with age (≤80 years and >80 years) as independent variable. Age 80 years and younger was used as reference level.
Multivariable regression analysis with age (≤80 years and >80 years) as independent variable. Age 80 years and younger was used as reference level. Results were adjusted for sex, prestroke mRS, admission National Institutes of Health Stroke Scale, baseline ASPECTS, treatment with intravenous thrombolysis, final modified Thrombolysis in Cerebral Infarction grade, and time between symptom onset or last known well to end of procedure.
χ2 Test.
Mann-Whitney U test.
Common ORs derived from ordinal logistic regression. Common ORs less than 1 indicate a shift in the distribution of 90-day mRS scores toward worse functional outcomes (higher mRS scores) in patients older than 80 years compared with patients aged 80 years and younger.
A multivariable regression analysis for symptomatic intracranial hemorrhage was not performed given the small number of cases (n = 28).
An age older than 80 years was associated with lower odds of achieving independent ambulation at 90 days compared with an age of 80 years and younger (aOR, 0.44; 95% CI, 0.23-0.82; P = .01). The odds of mortality were higher in patients older than 80 years compared with those aged 80 years and younger (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). In addition, lower prestroke mRS, lower admission NIHSS, and a final mTICI grade of 2b or 3 were associated with higher rates of independent ambulation and lower rates of mortality (eTable 1 in Supplement 1). Predicted probabilities of independent ambulation and death at 90 days stratified by age 80 years and younger and older than 80 years, prestroke mRS, admission NIHSS, and final mTICI grade are provided in Figure 2, with additional information in eFigure 3 in Supplement 1.
Figure 2. Predicted Probabilities for Independent Ambulation and Death Following Endovascular Thrombectomy Among Patients With Acute Ischemic Stroke With Large Infarct.
The predicted probabilities for independent ambulation at 90 days (A) and death within 90 days (B) are shown for given patient and treatment characteristics (age ≤80 years vs >80 years; prestroke modified Rankin Scale [mRS] score; admission National Institutes of Health Stroke Scale [NIHSS] score; and final modified Thrombolysis in Cerebral Infarction [mTICI] grade). The predicted probabilities are derived from the regression model in eTable 2 in Supplement 1.
Age and Clinical Benefit of Successful Reperfusion
After adjustment for age, a final mTICI grade of 2b or 3 was still associated with higher independent ambulation at 90 days (aOR, 4.95; 95% CI, 2.14-11.43; P < .001) and lower mortality within 90 days (aOR, 0.23; 95% CI, 0.13-0.43; P < .001) (eTable 3 in Supplement 1). The interaction term between age and successful reperfusion was not significant for independent ambulation (aOR, 0.69; 95% CI, 0.35-1.34; P = .27) or mortality (aOR, 0.92; 95% CI, 0.54-1.58; P = .77). Successful reperfusion had a higher predicted probability for independent ambulation compared with unsuccessful reperfusion in patients as old as 90 years (Figure 3A) and a lower predicted probability for death across all age levels (Figure 3B).
Figure 3. Age and Clinical Benefit of Successful Reperfusion.
Predicted probabilities with 95% CIs for independent ambulation at 90 days (A) and death within 90 days (B), stratified by age and reperfusion status. Results were adjusted for prestroke modified Rankin Scale score and admission National Institutes of Health Stroke Scale score. mTICI indicates modified Thrombolysis in Cerebral Infarction.
Discussion
This study provides an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic stroke with large infarct. Older age was strongly associated with poor functional outcomes in patients with ASPECTS of 0 to 5. Age was most informative when used in conjunction with prestroke mRS, admission NIHSS, and final mTICI grade. Age did not significantly modify the association of successful reperfusion with improved functional outcomes. The rates of independent ambulation and death for different age groups presented here could help clinicians inform decision-making for patients with acute ischemic stroke with large infarct. Particularly, our findings add insights for the subgroup of patients older than 80 years, who are underrepresented in randomized clinical trials but frequently encountered in clinical practice.
Patients with acute ischemic stroke and large infarct have very poor clinical outcomes even when receiving endovascular thrombectomy. Intravenous thrombolysis was administered in only 35.4% of our study population, which might be due to unfavorable factors serving as (relative) contraindications for intravenous thrombolysis (eg, late time window, high comorbidity). The rate of independent ambulation at 90 days was 28.9% in our study, which was comparable with the rates reported for the endovascular treatment groups of RESCUE-JAPAN LIMIT (31.0%),10 SELECT2 (37.9%),11 ANGEL-ASPECT (30.0%),12 and TENSION (31.0%).13 The rate of death within 90 days was 44.6% in the GSR-ET, which was comparable in SELECT2 (38.4%) and TENSION (40.0%) (eTable 4 in Supplement 1).
The association between age and functional outcomes in acute ischemic stroke is evident. This association is mediated by higher burden of comorbidities, greater cognitive impairment, and larger frailty levels in elderly patients, among other factors.19,20,21 As expected, functional outcomes differed significantly after stratification for age. We observed independent ambulation at 90 days in 1 of 2 patients aged 60 years and younger (56.4%), but in less than 1 of 6 patients older than 80 years (15.1%). Notably, nearly 2 of 3 patients older than 80 years with acute ischemic stroke and large infarct died within 90 days after endovascular thrombectomy (64.3%).
The question arises whether these extremely poor functional outcomes might justify the application of a fixed upper age limit for endovascular thrombectomy in acute ischemic stroke with large infarct. Importantly, a poor clinical prognosis does not generally preclude the treatment effect of an intervention. An upper age limit might simplify acute management and free up capacities of endovascular thrombectomy, but it would also underestimate the heterogeneity of aging across individuals. Outcome-modifying deficits do not accumulate as a linear function across a lifetime. Besides chronological age, clinical outcomes depend on additional patient and treatment characteristics. Accordingly, our analysis suggests that predicted probabilities for independent ambulation at 90 days range from 1% to 46% in patients older than 80 years with large infarct, depending on prestroke mRS, admission NIHSS, and final mTICI grade (Figure 2). Under specific conditions, patients older than 80 years could have a better clinical prognosis than younger patients receiving endovascular thrombectomy for large ischemic stroke.
Moreover, the implementation of an upper age limit requires evidence by randomized clinical trials dedicated to investigating the efficacy of endovascular thrombectomy over medical management alone in older populations. Such randomized clinical trials would have major issues with clinical equipoise, considering the enormous treatment effects of endovascular thrombectomy reported by the HERMES collaborators7 and the large core studies. In the HERMES meta-analysis,7 the treatment effect of endovascular thrombectomy was not modified by age, with even greater point estimates in patients aged 80 years and older (aOR, 3.68) compared with patients aged between 50 and 59 years (aOR, 2.85). Currently, in the absence of randomized data, retrospective studies are even more warranted to improve the accuracy of prognosis in acute ischemic stroke with large infarct, eg, by adding imaging markers for collateral status and cerebral edema formation.22,23,24
In summary, the decision for endovascular thrombectomy in patients with a large infarct should be made on a case-by-case basis, with age as one of several important factors. It must be considered that endovascular thrombectomy for large ischemic strokes imposes additional logistic and economic burdens on health care systems. Recent studies suggest cost-effectiveness in well-developed health care systems such as the United States.25,26,27 However, there will be much more debate in low-income and middle-income countries about allocation of thrombectomy capacities to older patients with established large infarct, considering the overall poor prognosis with high mortality.
Limitations
This study has several limitations. First, the retrospective study design might introduce selection bias, eg, due to missing data. It is reassuring to note that missing mRS scores were evenly distributed across the predefined age groups. Importantly, the retrospective study design without a medical treatment group did not allow us to estimate the treatment effect size of endovascular thrombectomy for large ischemic strokes in older patients. The lack of external validation lowers the generalizability of the main findings. Second, the definition of subgroups is pivotal, but to a certain extent arbitrary. Age groups were defined based on the HERMES meta-analysis,7 enabling a detailed analysis of patients older than 80 years. Third, clinical and imaging assessments were performed by local investigators at the respective study center and are therefore prone to substantial interrater variability. Fourth, the GSR-ET does not provide information about perfusion imaging such as ischemic core volume. To date, the role of perfusion imaging to select patients with large infarct for endovascular thrombectomy remains debatable. The TENSION trial13 suggested a treatment effect of endovascular thrombectomy in patients with ASPECTS of 3 to 5 solely guided by noncontrast CT or MRI without perfusion imaging. Fifth, the results presented here are primarily valid for acute stroke management within the German health care system. The rates of favorable functional outcomes after endovascular thrombectomy for large ischemic strokes in patients older than 80 years might be even lower in less developed health care systems.
Conclusions
In this study, age was associated with functional outcomes in patients with acute ischemic stroke and large infarct receiving endovascular thrombectomy. While functional outcomes are generally extremely poor in patients older than 80 years with ASPECTS of 0 to 5, they differ significantly after stratification for prestroke disability, severity of neurological impairment, and final mTICI grade. Considering current evidence, endovascular thrombectomy for acute ischemic stroke with large infarct should not be withheld based on an upper age limit. Age should be integrated within a multimodal approach to individualize treatment decisions in these highly affected patients with stroke. Our findings can assist neurologists and interventionalists in assessing the likely functional outcome of individual patients who receive endovascular thrombectomy for large ischemic strokes.
eFigure 1. Flowchart of Patient Inclusion and Exclusion Criteria
eFigure 2. Distribution of Age in Endovascular Thrombectomy for Acute Ischemic Stroke With Large Infarct
eFigure 3. Predicted Probabilities and 95% CIs for Independent Ambulation and Death in Endovascular Thrombectomy for Acute Ischemic Stroke With Large Infarct
eTable 1. Univariable and Multivariable Regression Analyses to Determine Factors Associated With Independent Ambulation at 90 Days, Death, and mRS Shift Toward Improved Functional Outcomes
eTable 2. Univariable and Multivariable Regression Analysis to Determine Factors Associated With Independent Ambulation at 90 Days and Death Within 90 Days
eTable 3. Univariable and Multivariable Regression Analysis to Determine Factors Associated With Independent Ambulation at 90 Days and Death Within 90 Days, With Age and Admission NIHSS Modeled as Continuous Variables
eTable 4. Overview of Published Randomized Clinical Trials
Nonauthor Collaborators
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure 1. Flowchart of Patient Inclusion and Exclusion Criteria
eFigure 2. Distribution of Age in Endovascular Thrombectomy for Acute Ischemic Stroke With Large Infarct
eFigure 3. Predicted Probabilities and 95% CIs for Independent Ambulation and Death in Endovascular Thrombectomy for Acute Ischemic Stroke With Large Infarct
eTable 1. Univariable and Multivariable Regression Analyses to Determine Factors Associated With Independent Ambulation at 90 Days, Death, and mRS Shift Toward Improved Functional Outcomes
eTable 2. Univariable and Multivariable Regression Analysis to Determine Factors Associated With Independent Ambulation at 90 Days and Death Within 90 Days
eTable 3. Univariable and Multivariable Regression Analysis to Determine Factors Associated With Independent Ambulation at 90 Days and Death Within 90 Days, With Age and Admission NIHSS Modeled as Continuous Variables
eTable 4. Overview of Published Randomized Clinical Trials
Nonauthor Collaborators
Data Sharing Statement