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Prestroke Conditions of Acute Ischemic Stroke Patients are Associated with Functional Outcome after Mechanical Thrombectomy
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Prestroke Conditions of Acute Ischemic Stroke Patients are Associated with Functional Outcome after Mechanical Thrombectomy Toshiaki Goda, MD,* Naoki Oyama, MD, PhD,* Takaya Kitano, MD,*,† Takanori Iwamoto, MD,* Shinji Yamashita, MD, PhD,* Hiroki Takai, MD,‡ Shunji Matsubara, MD, PhD,‡ Masaaki Uno, MD, PhD,‡ and Yoshiki Yagita, MD, PhD*
Background and Aim: Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear. Methods: A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes. Results: At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P < .001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P < .001). Conclusions: Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy. Key Words: Elderly patient—ischemic stroke—mechanical thrombectomy— prestroke modified Rankin scale © 2019 Elsevier Inc. All rights reserved.
Introduction From the *Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan; †Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan; and ‡Department of Neurosurgery, Kawasaki Medical School, Okayama, Japan. Received October 3, 2019; revision received November 6, 2019; accepted November 13, 2019. Grant Support: None. Address correspondence to Toshiaki Goda, MD, Department of Stroke Medicine, Kawasaki Medical School, 577, Matsushima, Kurashiki, Okayama, 701 0192, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter © 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104540
The usefulness of endovascular mechanical thrombectomy (MT) for acute ischemic stroke has recently been shown in several randomized controlled trials (RCTs). In the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke study, a meta-analysis of the first 5 positive RCTs, the prognostic outcome of patients was better in the MT group than in the medical treatment group.1 However, the patients in these RCTs were relatively young and maintained good prestroke activity of daily living (ADL). As a result, the current guidelines given by the American Heart Association/American Stroke Association
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indicate that the benefit of MT for patients with prestroke modified Rankin scale2 (mRS) greater than1 is uncertain, although there is no age limit.3 In contrast, some patients with large artery occlusion have poor prestroke conditions, such as older age and poor ADL, in the real world; in a rapidly aging society, the number of such patients who undergo MT is increasing markedly, but they were excluded in recent RCTs. Whether these patients can benefit from MT for acute ischemic stroke has not been clarified. Thus, in this study, we aimed to evaluate the prognostic effect of background factors, such as age and prestroke ADL, in patients treated with MT.
Materials and Methods Of 140 consecutive patients with acute ischemic stroke who underwent MT in our hospital between April 2015 and January 2019, 134 patients were evaluated using a mRS score at 90 days after stroke onset. Good outcome was defined as mRS 0-2 at 90 days, and poor outcome was defined as mRS 3-6 at 90 days. In addition, very poor outcome was defined as mRS 5-6 at 90 days. Demographic and clinical characteristics of patients were analyzed to assess their effects on clinical outcomes. The analyzed variables were age, sex, medical history (cerebral infarction/ transient ischemic attack, hypertension, diabetes mellitus, dyslipidemia, and atrial fibrillation), prestroke mRS, time from stroke onset to admission, initial National Institute of Health Stroke Scale (NIHSS) score,4 location of stroke, Alberta Stroke Program Early Computed Tomography Score for Diffusion-Weighted Imaging, including deep white matter lesions (DWI-ASPECTS),5 occluded vessels, whether intravenous thrombolysis with recombinant tissue plasminogen activator was performed, thrombectomy procedure, time from admission to groin puncture, time from groin puncture to recanalization, and modified Thrombolysis In Cerebral Infarction (mTICI) score.6 Poststroke mRS was determined based on postal questionnaires or telephone interviews unless patients were in the hospital or followed up in the outpatient department. Thrombectomy was performed using a stent retriever and/or the Penumbra system (Penumbra, Alameda, CA) as the first choice. We performed percutaneous transluminal angioplasty, intra-arterial injection of urokinase, or other procedures depending on the case. The selection of devices was according to the discretion of each operator. All clinical information was retrospectively collected from medical records. The study protocol complied with the Declaration of Helsinki recommendations and was approved by the Ethics Committee of the Kawasaki Medical School Hospital. The procedures complied with institutional guidelines. Given the retrospective enrollment, patient consent for participation was waived.
Statistical Analysis Differences between groups were tested using Fisher’s exact tests for categorical variables and the Mann-Whitney U-test for continuous variables. To assess the independent contribution of each variable, we performed a multiple logistic regression analysis including all clinical variables with P less than .1 in the univariate analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. P less than .05 was considered statistically significant. All analyses were conducted using EZR7 (version 1.33, Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, EZR is a modified version of R Commander designed to add statistical functions frequently used in biostatistics.
Results At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome (mRS 0-2) and 62.7% (84 of 134) had a poor outcome (mRS 3-6). Table 1 shows the baseline characteristics of patients in both groups. In the univariate analysis, lower age (median 72 versus 79.5 years, P < .001), male sex (74.0% versus 39.3%, P < .001), lower prestroke mRS (median 0 versus 2, P < .001), lower initial NIHSS score (median 15 versus 19, P = .001), shorter time from groin puncture to recanalization (median 65 versus 95 min, P = .008), and mTICI 2b or 3 (86.0% versus 63.1%, P = .005) were associated with a good outcome. The multivariate analysis showed that only prestroke mRS (OR .39, 95% CI .22-.67, P < .001) was independently associated with a good outcome as a patient background factor (Table 2). In the analysis of patients with prestroke mRS 0-1, 55.4% (46 of 83) had a good outcome (Fig 1A). Of these, 57.9% (33 of 57) of patients aged less than 80 years and 50% (13 of 26) of those aged greater than or equal to 80 years had a good outcome, and there was no significant difference between the 2 (P = .64) (Fig 1B). In the analysis of patients with prestroke mRS greater than or equal to 2, 13.7% (7 of 51) could maintain their prestroke mRS at 90 days, which was lesser than those with prestroke mRS 0-1 (20.5%, 17 of 83), although the difference was not significant (P = .36). A total of 54.9% (28 of 51) of patients with prestroke mRS greater than or equal to 2 had a very poor outcome, mRS 5-6 at 90 days, which was significantly higher than those with prestroke mRS 0-1 [21.7% (18 of 83), P < .001] (Fig 1A). In patients with prestroke mRS greater than or equal to 2, 57.9% (11 of 19) of those aged less than 80 years and 53.1% (17 of 32) of those aged greater than or equal to 80 years had a very poor outcome, and there was no significant difference between the 2 (P = .78) (Fig. 1C). The main causes of prestroke mRS greater than or equal to 2 were a history of stroke (21 of 51), dementia (19 of 51), musculoskeletal diseases (17 of 51), cardiovascular
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Table 1. Baseline characteristics of patients
Age, years, median (IQR) Male Medical history Ischemic stroke or TIA Hypertension Diabetes mellitus Dyslipidemia Atrial fibrillation Prestroke mRS, median (IQR) Onset to admission, min, median (IQR) Initial NIHSS, median (IQR) Location of stroke in left hemisphere DWI-ASPECTS, median (IQR) ICA or M1 occlusion Treatment with intravenous alteplase Thrombectomy procedure Stent retriever only Aspiration only Combined Admission to puncture, min, median (IQR) Puncture to recanalization, min, median (IQR) modified TICI score 2b or 3
All (n = 134)
mRS 0-2 at 90 days (n = 50)
mRS 3-6 at 90 days (n = 84)
P value
77 (70-84) 70 (52.2%)
72 (67.3-82) 37 (74.0%)
79.5 (73-86) 33 (39.3%)
<.001 <.001
36 (26.9%) 79 (59.0%) 27 (20.1%) 31 (23.1%) 56 (41.8%) 0 (0-3) 133 (69-256) 18 (12.3-23) 57 (42.5%) 7 (5-8) 85 (63.4%) 49 (36.6%)
12 (24.0%) 28 (56.0%) 8 (16.0%) 12 (24.0%) 16 (32.0%) 0 (0-0) 158 (60-227) 15 (6.5-21) 23 (46.0%) 8 (6-8.5) 32 (64.0%) 19 (38.0%)
24 (28.6%) 51 (60.7%) 19 (22.6%) 19 (22.6%) 40 (47.6%) 2 (0-3) 133 (76-271) 19 (15-24) 34 (40.5%) 6 (5-8) 53 (63.1%) 30 (35.7%)
.69 .72 .38 >.99 .10 <.001 .49 .001 .71 .090 >.99 .85
24 (17.9%) 35 (26.1%) 57 (42.5%) 74 (62-104) 86 (59-133) 96 (71.6%)
7 (14.0%) 15 (30.0%) 18 (36.0%) 74 (62-103) 65 (50-104) 43 (86.0%)
17 (20.2%) 20 (23.8%) 39 (46.4%) 75 (62-104) 95 (70-153) 53 (63.1%)
.63 .29 .56 .78 .008 .005
Data are presented as n (%) unless otherwise specified. Abbreviations: DWI-ASPECTS, Alberta Stroke Program Early Computed Tomography Score for Diffusion-Weighted Imaging; ICA, internal carotid artery; IQR, interquartile range; M1, horizontal portion of middle cerebral artery; mRS, modified Rankin scale; NIHSS, National Institute of Health Stroke Scale; TIA, transient ischemic attack; TICI, thrombolysis in cerebral infarction.
diseases (14 of 51), and other severe conditions (12 of 51) such as advanced cancer, neurodegenerative diseases, and age-related frailty. The main causes of mRS 5-6 at 90 days are unsuccessful recanalization (11 of 28), massive ischemic stroke despite successful recanalization (7 of 28), perioperative complications (3 of 28), and poststroke infectious complications (8 of 28).
Discussion We aimed to clarify whether patients with poor prestroke conditions, such as older age and low ADL, can Table 2. Multiple logistic regression analysis for predictors of good outcome (mRS 0-2 at 90 days)
Age, years Male Prestroke mRS DWI-ASPECTS Initial NIHSS Puncture to recanalization per 10-min increase modified TICI score 2b or 3
OR (95% CI)
P value
.96 (.91-1.01) 2.94 (.98-8.89) .39 (.22-.67) 1.12 (.86-1.45) .91 (.84-.99) .91 (.81-1.02)
.13 .055 <.001 .41 .043 .096
3.77 (.84-16.8)
.082
Abbreviations: CI, confidence interval; mRS, modified Rankin Scale; NIHSS, National Institute of Health Stroke Scale; OR, odds ratio.
benefit from MT. This study suggests that prestroke mRS has a strong influence on the prognosis of patients after MT regardless of their age. More than half of patients with prestroke mRS 0-1 had a good outcome even if they aged greater than or equal to 80 years. In patients with prestroke mRS greater than or equal to 2, 13.7% (7 of 51) could maintain their prestroke mRS at 90 days, which might justify use of MT in these patients. However, more than half of patients with prestroke mRS greater than or equal to 2 were graded as mRS 5-6 at 90 days, even if they were relatively young. In patients with prestroke mRS greater than or equal to 2, we should select candidates for MT more carefully. In the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke study, although the prognostic outcome of patients was better in the MT group than in the medical treatment group even in patients aged greater than or equal to 80 years, older age was reported to be a strong independent predictor of poor prognosis. Speculative reasons for poor prognosis in elderly patients include high prevalence of elongated and tortuous vessels, which makes catheter access difficult8; they are less likely to recover through rehabilitation and more likely to suffer from complications after stroke.9 However, the relationship between older age and poor prognosis has not been fully investigated in the real world. Some studies indicated that clinical outcomes in elderly patients were
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returned to their prestroke condition at 90 days after MT was small compared with patients with prestroke mRS 02, and the mortality rate at 90 days was 50%.13 In the present study, more than half of patients with prestroke mRS greater than or equal to 2 had mRS 5-6 at 90 days, which is compatible with that of the previous study.13 The main causes of prestroke mRS greater than or equal to 2 were severe underlying diseases, such as a history of stroke, dementia, musculoskeletal diseases, and cardiovascular diseases. The possible reason for the significant correlation between prestroke mRS greater than or equal to 2 and mRS 5-6 at 90 days is that patients with severe underlying diseases are more likely to suffer from poststroke complications, such as pneumonia, which leads to poor functional prognosis.14 Worsening of underlying diseases, such as dementia and cardiovascular diseases during acute stroke treatment might also limit rehabilitation effects. Moreover, patients with a history of stroke or musculoskeletal diseases often significantly decrease their ADL level by losing their functions of healthy side, resulting in bilateral disability. It remains controversial whether MT should be positively performed for patients with prestroke mRS greater than or equal to 2. This study has several limitations. First, this was a retrospective, single-center study with small number of patients. Further prospective, multicenter studies are needed to confirm our preliminary results. Second, ischemic stroke patients who did not undergo MT were not included in this study. Because we did not have a control group, it is not possible to determine whether MT is beneficial for patients with prestroke mRS greater than or equal to 2 compared with best medical care.
Summary and Conclusion
Figure 1. Percentages of patients with scores on the modified Rankin Scale (mRS) at 90 days. A: Distribution of scores according to prestroke mRS. B: Distribution of scores in patients with prestroke mRS 0-1. C: Distribution of scores in patients with prestroke mRS 2-4.
poorer than those in young patients after MT,10-12 but patients with prestroke mRS greater than or equal to 2 were included in these studies, which might have led to unfavorable outcomes in elderly patients. Our study is significant in that it suggests the effectiveness of MT for patients with prestroke mRS 0-1 aged greater than or equal to 80 years as well as those aged less than 80 years in real-world practice. Data on patients with prestroke mRS greater than or equal to 2 are limited in each RCT that shows the efficacy of MT. One previous cohort study showed that the proportion of patients with prestroke mRS 3 and 4 who
Patients with prestroke mRS 0-1 are expected to have a good prognosis after MT even if they are greater than or equal to 80 years old, and old age should not be used as exclusion criteria for MT in patients with acute large vessel occlusion. Patients with prestroke mRS greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for MT.
Acknowledgment The authors thank Editage (www.editage.jp) for English language editing.
Conflict of Interest The authors have no conflict of interests to declare.
References 1. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a
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meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723-1731. van Swieten JC, Koudstaal PJ, Visser MC, et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988;19:604-607. Ren Z, Mokin M, Bauer CT, et al. Indications for mechanical thrombectomy too wide or too narrow? World Neurosurg 2019;127:492-499. Lyden P, Lu M, Jackson C, et al. Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. NINDS tPA Stroke Trial Investigators.. Stroke 1999;30:2347-2354. Kawano H, Hirano T, Nakajima M, et al. Modified ASPECTS for DWI including deep white matter lesions predicts subsequent intracranial hemorrhage. J Neurol 2012;259:2045-2052. Zaidat OO, Yoo AJ, Khatri P, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013;44:2650-2663. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013;48:452-458. Ribo M, Flores A, Rubiera M, et al. Difficult catheter access to the occluded vessel during endovascular treatment of
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acute ischemic stroke is associated with worse clinical outcome. J Neurointerv Surg 2013;5:i70-i73. Ford GA, Ahmed N, Azevedo E, et al. Intravenous alteplase for stroke in those older than 80 years old. Stroke 2010;41:2568-2574. Parrilla G, Carreon E, Zamarro J, et al. Recanalization and mortality rates of thrombectomy with stent-retrievers in octogenarian patients with acute ischemic stroke. Cardiovasc Intervent Radiol 2015;38:288-294. Castonguay AC, Zaidat OO, Novakovic R, et al. Influence of age on clinical and revascularization outcomes in the North American Solitaire Stent-Retriever Acute Stroke Registry. Stroke 2014;45:3631-3636. Son S, Kang DH, Hwang YH, et al. Efficacy, safety, and clinical outcome of modern mechanical thrombectomy in elderly patients with acute ischemic stroke. Acta Neurochir 2017;159:1663-1669. Seker F, Pfaff J, Sch€ onenberger S, et al. Clinical outcome after thrombectomy in patients with stroke with premorbid modified Rankin scale scores of 3 and 4: a cohort study with 136 patients. AJNR Am J Neuroradiol 2019;40:283-286. Finlayson O, Kapral M, Hall R, et al. Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke. Neurology 2011;77:1338-1345.
Prestroke Conditions of Acute Ischemic Stroke Patients are Associated with Functional Outcome after Mechanical Thrombectomy Toshiaki Goda, MD,* Naoki Oyama, MD, PhD,* Takaya Kitano, MD,*,† Takanori Iwamoto, MD,* Shinji Yamashita, MD, PhD,* Hiroki Takai, MD,‡ Shunji Matsubara, MD, PhD,‡ Masaaki Uno, MD, PhD,‡ and Yoshiki Yagita, MD, PhD*
Background and Aim: Mechanical thrombectomy was demonstrated to be useful for acute ischemic stroke. However, whether it is beneficial for patients with poor prestroke conditions, such as older adults and those with low activity of daily living, is unclear. Methods: A total of 134 patients who underwent mechanical thrombectomy in our hospital between April 2015 and January 2019 were retrospectively evaluated. Good outcome was defined as modified Rankin scale score of 0-2 at 90 days after stroke onset. Several factors were analyzed to assess their effects on clinical outcomes. Results: At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome. Prestroke modified Rankin scale score was independently associated with a good outcome (odds ratio .39, 95% confidence interval .22-.67, P < .001). In patients with prestroke modified Rankin scale score 0-1, 55.4% (46 of 83) had a good outcome, and no significant difference in prognosis was found between patients aged less than 80 years and those aged greater than or equal to 80 years (P = .64). More than half the patients with prestroke modified Rankin scale score greater than or equal to 2 were graded as modified Rankin scale score 5-6 at 90 days regardless of age, which was significantly higher than those with prestroke modified Rankin scale score 0-1 (P < .001). Conclusions: Patients with prestroke modified Rankin scale score 0-1 are expected to have a good prognosis after mechanical thrombectomy even if aged greater than or equal to 80 years. Patients with prestroke modified Rankin scale score greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for mechanical thrombectomy. Key Words: Elderly patient—ischemic stroke—mechanical thrombectomy— prestroke modified Rankin scale © 2019 Elsevier Inc. All rights reserved.
Introduction From the *Department of Stroke Medicine, Kawasaki Medical School, Okayama, Japan; †Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan; and ‡Department of Neurosurgery, Kawasaki Medical School, Okayama, Japan. Received October 3, 2019; revision received November 6, 2019; accepted November 13, 2019. Grant Support: None. Address correspondence to Toshiaki Goda, MD, Department of Stroke Medicine, Kawasaki Medical School, 577, Matsushima, Kurashiki, Okayama, 701 0192, Japan. E-mail: [email protected]. 1052-3057/$ - see front matter © 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104540
The usefulness of endovascular mechanical thrombectomy (MT) for acute ischemic stroke has recently been shown in several randomized controlled trials (RCTs). In the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke study, a meta-analysis of the first 5 positive RCTs, the prognostic outcome of patients was better in the MT group than in the medical treatment group.1 However, the patients in these RCTs were relatively young and maintained good prestroke activity of daily living (ADL). As a result, the current guidelines given by the American Heart Association/American Stroke Association
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, No. && (&&), 2019: 104540
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indicate that the benefit of MT for patients with prestroke modified Rankin scale2 (mRS) greater than1 is uncertain, although there is no age limit.3 In contrast, some patients with large artery occlusion have poor prestroke conditions, such as older age and poor ADL, in the real world; in a rapidly aging society, the number of such patients who undergo MT is increasing markedly, but they were excluded in recent RCTs. Whether these patients can benefit from MT for acute ischemic stroke has not been clarified. Thus, in this study, we aimed to evaluate the prognostic effect of background factors, such as age and prestroke ADL, in patients treated with MT.
Materials and Methods Of 140 consecutive patients with acute ischemic stroke who underwent MT in our hospital between April 2015 and January 2019, 134 patients were evaluated using a mRS score at 90 days after stroke onset. Good outcome was defined as mRS 0-2 at 90 days, and poor outcome was defined as mRS 3-6 at 90 days. In addition, very poor outcome was defined as mRS 5-6 at 90 days. Demographic and clinical characteristics of patients were analyzed to assess their effects on clinical outcomes. The analyzed variables were age, sex, medical history (cerebral infarction/ transient ischemic attack, hypertension, diabetes mellitus, dyslipidemia, and atrial fibrillation), prestroke mRS, time from stroke onset to admission, initial National Institute of Health Stroke Scale (NIHSS) score,4 location of stroke, Alberta Stroke Program Early Computed Tomography Score for Diffusion-Weighted Imaging, including deep white matter lesions (DWI-ASPECTS),5 occluded vessels, whether intravenous thrombolysis with recombinant tissue plasminogen activator was performed, thrombectomy procedure, time from admission to groin puncture, time from groin puncture to recanalization, and modified Thrombolysis In Cerebral Infarction (mTICI) score.6 Poststroke mRS was determined based on postal questionnaires or telephone interviews unless patients were in the hospital or followed up in the outpatient department. Thrombectomy was performed using a stent retriever and/or the Penumbra system (Penumbra, Alameda, CA) as the first choice. We performed percutaneous transluminal angioplasty, intra-arterial injection of urokinase, or other procedures depending on the case. The selection of devices was according to the discretion of each operator. All clinical information was retrospectively collected from medical records. The study protocol complied with the Declaration of Helsinki recommendations and was approved by the Ethics Committee of the Kawasaki Medical School Hospital. The procedures complied with institutional guidelines. Given the retrospective enrollment, patient consent for participation was waived.
Statistical Analysis Differences between groups were tested using Fisher’s exact tests for categorical variables and the Mann-Whitney U-test for continuous variables. To assess the independent contribution of each variable, we performed a multiple logistic regression analysis including all clinical variables with P less than .1 in the univariate analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. P less than .05 was considered statistically significant. All analyses were conducted using EZR7 (version 1.33, Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, EZR is a modified version of R Commander designed to add statistical functions frequently used in biostatistics.
Results At 90 days after stroke onset, 37.3% (50 of 134) of patients had a good outcome (mRS 0-2) and 62.7% (84 of 134) had a poor outcome (mRS 3-6). Table 1 shows the baseline characteristics of patients in both groups. In the univariate analysis, lower age (median 72 versus 79.5 years, P < .001), male sex (74.0% versus 39.3%, P < .001), lower prestroke mRS (median 0 versus 2, P < .001), lower initial NIHSS score (median 15 versus 19, P = .001), shorter time from groin puncture to recanalization (median 65 versus 95 min, P = .008), and mTICI 2b or 3 (86.0% versus 63.1%, P = .005) were associated with a good outcome. The multivariate analysis showed that only prestroke mRS (OR .39, 95% CI .22-.67, P < .001) was independently associated with a good outcome as a patient background factor (Table 2). In the analysis of patients with prestroke mRS 0-1, 55.4% (46 of 83) had a good outcome (Fig 1A). Of these, 57.9% (33 of 57) of patients aged less than 80 years and 50% (13 of 26) of those aged greater than or equal to 80 years had a good outcome, and there was no significant difference between the 2 (P = .64) (Fig 1B). In the analysis of patients with prestroke mRS greater than or equal to 2, 13.7% (7 of 51) could maintain their prestroke mRS at 90 days, which was lesser than those with prestroke mRS 0-1 (20.5%, 17 of 83), although the difference was not significant (P = .36). A total of 54.9% (28 of 51) of patients with prestroke mRS greater than or equal to 2 had a very poor outcome, mRS 5-6 at 90 days, which was significantly higher than those with prestroke mRS 0-1 [21.7% (18 of 83), P < .001] (Fig 1A). In patients with prestroke mRS greater than or equal to 2, 57.9% (11 of 19) of those aged less than 80 years and 53.1% (17 of 32) of those aged greater than or equal to 80 years had a very poor outcome, and there was no significant difference between the 2 (P = .78) (Fig. 1C). The main causes of prestroke mRS greater than or equal to 2 were a history of stroke (21 of 51), dementia (19 of 51), musculoskeletal diseases (17 of 51), cardiovascular
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Table 1. Baseline characteristics of patients
Age, years, median (IQR) Male Medical history Ischemic stroke or TIA Hypertension Diabetes mellitus Dyslipidemia Atrial fibrillation Prestroke mRS, median (IQR) Onset to admission, min, median (IQR) Initial NIHSS, median (IQR) Location of stroke in left hemisphere DWI-ASPECTS, median (IQR) ICA or M1 occlusion Treatment with intravenous alteplase Thrombectomy procedure Stent retriever only Aspiration only Combined Admission to puncture, min, median (IQR) Puncture to recanalization, min, median (IQR) modified TICI score 2b or 3
All (n = 134)
mRS 0-2 at 90 days (n = 50)
mRS 3-6 at 90 days (n = 84)
P value
77 (70-84) 70 (52.2%)
72 (67.3-82) 37 (74.0%)
79.5 (73-86) 33 (39.3%)
<.001 <.001
36 (26.9%) 79 (59.0%) 27 (20.1%) 31 (23.1%) 56 (41.8%) 0 (0-3) 133 (69-256) 18 (12.3-23) 57 (42.5%) 7 (5-8) 85 (63.4%) 49 (36.6%)
12 (24.0%) 28 (56.0%) 8 (16.0%) 12 (24.0%) 16 (32.0%) 0 (0-0) 158 (60-227) 15 (6.5-21) 23 (46.0%) 8 (6-8.5) 32 (64.0%) 19 (38.0%)
24 (28.6%) 51 (60.7%) 19 (22.6%) 19 (22.6%) 40 (47.6%) 2 (0-3) 133 (76-271) 19 (15-24) 34 (40.5%) 6 (5-8) 53 (63.1%) 30 (35.7%)
.69 .72 .38 >.99 .10 <.001 .49 .001 .71 .090 >.99 .85
24 (17.9%) 35 (26.1%) 57 (42.5%) 74 (62-104) 86 (59-133) 96 (71.6%)
7 (14.0%) 15 (30.0%) 18 (36.0%) 74 (62-103) 65 (50-104) 43 (86.0%)
17 (20.2%) 20 (23.8%) 39 (46.4%) 75 (62-104) 95 (70-153) 53 (63.1%)
.63 .29 .56 .78 .008 .005
Data are presented as n (%) unless otherwise specified. Abbreviations: DWI-ASPECTS, Alberta Stroke Program Early Computed Tomography Score for Diffusion-Weighted Imaging; ICA, internal carotid artery; IQR, interquartile range; M1, horizontal portion of middle cerebral artery; mRS, modified Rankin scale; NIHSS, National Institute of Health Stroke Scale; TIA, transient ischemic attack; TICI, thrombolysis in cerebral infarction.
diseases (14 of 51), and other severe conditions (12 of 51) such as advanced cancer, neurodegenerative diseases, and age-related frailty. The main causes of mRS 5-6 at 90 days are unsuccessful recanalization (11 of 28), massive ischemic stroke despite successful recanalization (7 of 28), perioperative complications (3 of 28), and poststroke infectious complications (8 of 28).
Discussion We aimed to clarify whether patients with poor prestroke conditions, such as older age and low ADL, can Table 2. Multiple logistic regression analysis for predictors of good outcome (mRS 0-2 at 90 days)
Age, years Male Prestroke mRS DWI-ASPECTS Initial NIHSS Puncture to recanalization per 10-min increase modified TICI score 2b or 3
OR (95% CI)
P value
.96 (.91-1.01) 2.94 (.98-8.89) .39 (.22-.67) 1.12 (.86-1.45) .91 (.84-.99) .91 (.81-1.02)
.13 .055 <.001 .41 .043 .096
3.77 (.84-16.8)
.082
Abbreviations: CI, confidence interval; mRS, modified Rankin Scale; NIHSS, National Institute of Health Stroke Scale; OR, odds ratio.
benefit from MT. This study suggests that prestroke mRS has a strong influence on the prognosis of patients after MT regardless of their age. More than half of patients with prestroke mRS 0-1 had a good outcome even if they aged greater than or equal to 80 years. In patients with prestroke mRS greater than or equal to 2, 13.7% (7 of 51) could maintain their prestroke mRS at 90 days, which might justify use of MT in these patients. However, more than half of patients with prestroke mRS greater than or equal to 2 were graded as mRS 5-6 at 90 days, even if they were relatively young. In patients with prestroke mRS greater than or equal to 2, we should select candidates for MT more carefully. In the Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke study, although the prognostic outcome of patients was better in the MT group than in the medical treatment group even in patients aged greater than or equal to 80 years, older age was reported to be a strong independent predictor of poor prognosis. Speculative reasons for poor prognosis in elderly patients include high prevalence of elongated and tortuous vessels, which makes catheter access difficult8; they are less likely to recover through rehabilitation and more likely to suffer from complications after stroke.9 However, the relationship between older age and poor prognosis has not been fully investigated in the real world. Some studies indicated that clinical outcomes in elderly patients were
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returned to their prestroke condition at 90 days after MT was small compared with patients with prestroke mRS 02, and the mortality rate at 90 days was 50%.13 In the present study, more than half of patients with prestroke mRS greater than or equal to 2 had mRS 5-6 at 90 days, which is compatible with that of the previous study.13 The main causes of prestroke mRS greater than or equal to 2 were severe underlying diseases, such as a history of stroke, dementia, musculoskeletal diseases, and cardiovascular diseases. The possible reason for the significant correlation between prestroke mRS greater than or equal to 2 and mRS 5-6 at 90 days is that patients with severe underlying diseases are more likely to suffer from poststroke complications, such as pneumonia, which leads to poor functional prognosis.14 Worsening of underlying diseases, such as dementia and cardiovascular diseases during acute stroke treatment might also limit rehabilitation effects. Moreover, patients with a history of stroke or musculoskeletal diseases often significantly decrease their ADL level by losing their functions of healthy side, resulting in bilateral disability. It remains controversial whether MT should be positively performed for patients with prestroke mRS greater than or equal to 2. This study has several limitations. First, this was a retrospective, single-center study with small number of patients. Further prospective, multicenter studies are needed to confirm our preliminary results. Second, ischemic stroke patients who did not undergo MT were not included in this study. Because we did not have a control group, it is not possible to determine whether MT is beneficial for patients with prestroke mRS greater than or equal to 2 compared with best medical care.
Summary and Conclusion
Figure 1. Percentages of patients with scores on the modified Rankin Scale (mRS) at 90 days. A: Distribution of scores according to prestroke mRS. B: Distribution of scores in patients with prestroke mRS 0-1. C: Distribution of scores in patients with prestroke mRS 2-4.
poorer than those in young patients after MT,10-12 but patients with prestroke mRS greater than or equal to 2 were included in these studies, which might have led to unfavorable outcomes in elderly patients. Our study is significant in that it suggests the effectiveness of MT for patients with prestroke mRS 0-1 aged greater than or equal to 80 years as well as those aged less than 80 years in real-world practice. Data on patients with prestroke mRS greater than or equal to 2 are limited in each RCT that shows the efficacy of MT. One previous cohort study showed that the proportion of patients with prestroke mRS 3 and 4 who
Patients with prestroke mRS 0-1 are expected to have a good prognosis after MT even if they are greater than or equal to 80 years old, and old age should not be used as exclusion criteria for MT in patients with acute large vessel occlusion. Patients with prestroke mRS greater than or equal to 2 might have an extremely poor prognosis, and we should be more careful in selecting candidates for MT.
Acknowledgment The authors thank Editage (www.editage.jp) for English language editing.
Conflict of Interest The authors have no conflict of interests to declare.
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