Endovascular Treatment and Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability or Dementia: A Scientific Statement From the American Heart Association/American Stroke Association
Abstract
Patients with premorbid disability or dementia have generally been excluded from randomized controlled trials of reperfusion therapies such as thrombolysis and endovascular therapy for acute ischemic stroke. Consequently, stroke physicians face treatment dilemmas in caring for such patients. In this scientific statement, we review the literature on acute ischemic stroke in patients with premorbid disability or dementia and propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of premorbid disability or dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies have also helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have helped demonstrate the comparable safety of endovascular therapy in patients with premorbid disability or dementia and in those without, complementing similar data on thrombolysis. These data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.
Acute ischemic stroke is a leading cause of disability worldwide, with 30% to 40% of survivors developing new poststroke disability.1 Thus, the primary focus of reperfusion therapies is the prevention of stroke-related disability. However, many patients presenting with an acute ischemic stroke have preexisting disability present before their stroke, also known as prestroke or premorbid disability. The World Health Organization estimates that 15% of the world’s population lives with disability; in the United States, 22% of adults report some disability.1,2 Whereas one may reflexively associate the term disability with physical disability, disability can also be intellectual or cognitive. The most common type of acquired, premorbid cognitive disability seen in the setting of ischemic stroke is dementia. Observational studies indicate that preexisting disabilities exist in approximately one-third of patients with ischemic stroke,3 whereas preexisting dementia is present in approximately one tenth.4
Unfortunately, there is an absence of definitive evidence for the use of acute stroke therapies such as thrombolysis and endovascular therapy (EVT) in these patients with premorbid disability or dementia because they have conventionally been excluded from randomized controlled trials.5,6 In addition, because these treatments cannot restore patients beyond their premorbid state, they will, at best, result in the patients living with the same or worse disability. Consequently, stroke physicians face treatment dilemmas in caring for such patients.7 Indeed, premorbid disability is a common reason for exclusion of patients from thrombolysis in routine practice,8 and patients with dementia are less likely to receive thrombolysis or stroke unit care.9 Current guidelines do not provide a framework for addressing this problem. European guidelines recommend that patients selected for acute stroke therapies should have a prestroke modified Rankin Scale (mRS) score of 0 to 1 while noting the lack of evidence for patients with an mRS score ≥2.10 The European Stroke Organization’s recently updated EVT guidelines again note the uncertain benefit for patients with significant prestroke disability, particularly those >80 years of age.11 American Heart Association guidelines state that prestroke disability does not seem to increase the risk of postthrombolysis hemorrhage and that reperfusion therapies may be reasonable in selected cases, but they also state that treatment may be associated with less neurological improvement and higher mortality.12,13 Therefore, our aim was to review the literature on acute ischemic stroke in patients with premorbid disability/dementia and to propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations.
Our literature search strategy is described in the Supplemental Material.
Defining the Problem
To understand the problem, it is critical to define premorbid disability and dementia. Exclusions of these patients from trials generally have been defined with the use of functional outcome measures; for example, the seminal trials of EVT generally excluded patients with an mRS score ≥2 or Barthel Index score <95.6 Although such definitions seem pragmatic, they do not necessarily capture how disability and dementia manifest in practice. Such definitions also vary by the choice of rating scale or the threshold for defining the preexisting disability within the same scoring tool.14,15 The most widely accepted definition of disability comes from the World Health Organization’s International Classification of Impairments, Disabilities and Handicaps.16 Disability here means “any restriction or lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a human being.” According to this definition, disability derives from impairment, which in turn is defined as “any loss or abnormality of psychological, physiological or anatomical structure or function.” Disability may or may not result in handicap, which is defined as “a disadvantage for a given individual that limits or prevents the fulfillment of a role that is normal.”16 This is a crucial point that can be easily overlooked when considering the implications of disability in stroke care: Disability need not inevitably result in handicap, and handicap is potentially preventable by means of technological or societal adaptations and accommodations. The distinction is important to acknowledge; the mRS, the most favored primary outcome measure in acute stroke trials, mixes impairment, disability, and handicap and overvalues physical disability relative to cognitive disability.16 Dementia, also known as major neurocognitive disorder, is defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition as evidence of substantial cognitive decline from a previous level of performance in ≥1 domain that is based on the concerns of the patient, a knowledgeable informant, or the clinician, with a decline in neurocognitive performance (typically on formal testing) and resulting in the patient requiring at least some assistance with instrumental activities of daily living.17
With the complexity of the definitions above, it is apparent that, in the setting of acute stroke, the identification or evaluation of prestroke disability or dementia involves considerable uncertainty because the quality of available information is almost certainly inadequate to meet these definitions.18 Scales like the mRS, originally intended for poststroke measurement with input from patients and caregivers,19 are often constrained in the acute stroke setting by limited access to reliable informants and by the patient’s inability to communicate as a result of the stroke. This forces physicians to rely on incomplete or inaccurate proxy reports or medical records.20,21 The critical time constraints of acute stroke therapies also rule out any formal assessment of prior cognitive decline, so the physician relies on either a medical record of a dementia diagnosis or a report from the patient or family member.
Besides these limitations of existing tools to evaluate premorbid disability or dementia in practice (Supplemental Table 1), we must consider intersectionality, a crucial sociological concept that is only now gaining traction in the stroke literature.22 Intersectionality refers to the interconnected nature of categorizations such as disability, race, class, and sex, which create overlapping and interdependent systems of discrimination or advantage. Applying an intersectionality lens to the prevalent functional status-based (eg, mRS-based) definitions of disability in stroke trials, we find that exclusion by premorbid disability likely also unintentionally promotes exclusion by other demographic factors. For example, in the population-based OXVASC (Oxford Vascular Study), patients with premorbid disability defined by an mRS score ≥2 were generally older, more often female, and more likely to be socioeconomically deprived, even after adjustment for comorbidities.3,23 This sex difference in premorbid mRS score also has been shown in major clinical trials such as ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), SCAST (Scandinavian Candesartan Acute Stroke Trial), and HeadPoST (Head Positioning in Acute Stroke Trial).24 As for age and disability, we can consider, for example, the largest thrombolysis trial in acute ischemic stroke, the third International Stroke Trial, which encouraged enrollment of older patients but still excluded those with an mRS score ≥2, calling into question how representative these patients were of the typical older stroke population.25 Similar considerations also apply for dementia. In addition to the known association between dementia and increasing age, there are racial differences; the prevalence and incidence of dementia are higher among Black people in the United States than among non-Hispanic White people.26,27 Therefore, exclusion of patients by premorbid disability or dementia may limit the generalizability of our treatment evidence for older patients, women, and even certain races.
Implications of Prestroke Disability and Dementia on the Prognosis of Acute Ischemic Stroke
The presence of preexisting disability and dementia can affect decision-making and outcomes as the patient moves through the stroke systems of care. This includes difficulties in the prehospital, transfer, triage, and in-hospital to posthospital processes. In the prehospital setting, there is often a delay in recognition of acute stroke symptoms because patients may be unable to call for help. Relatives and first responders also may have difficulty recognizing new symptoms or may be less inclined to seek medical attention in the setting of preexisting illness.28,29 Once patients do present, their prior deficits confound the assessment of the stroke severity scale. This confounding often leads to a higher severity assessment with the resulting perception that they will have a worse outcome.4,30,31 These patients are less likely to receive thrombolysis. There are documented delays in treatment times for those patients with disability who are treated with thrombolysis or with endovascular treatment.9,31–34 Such delays are known to adversely affect stroke outcomes. Once admitted to the hospital, these patients are less likely to receive defect-free evidence-based stroke care.31,34,35 There are fewer admissions to stroke units and fewer investigations for secondary stroke prevention in patients with prestroke disability or dementia.30,31,34 In addition, this population has a 3 to 4 times higher nosocomial infection rate,36 a longer average hospital stay,36 and a 3 to 5.4 times higher odds of in-hospital mortality,37,38 with a higher rate of withdrawal of care.36
Patients with preexisting dementia or disability who are not treated and who survive to discharge have a higher probability of being discharged to a nursing home or being institutionalized.9,39,40 The long-term consequences and social care costs of the additional disability of untreated stroke in patients with preexisting neurological deficits are staggering.3,30,31,38 In the OXVASC,3 79% of patients with prestroke disability were alive at 3 months, and these patients lived an average of 1.35 years (95% CI, 1.20–1.51) after stroke. Among these patients, 30.8% did not return to community dwelling and required new institutionalization. Each added degree of poststroke disability (ΔmRS score at 3 months after stroke) had a worse outcome, with the hazard ratio for 5-year mortality/institutionalization ranging from 1.62 to 5.45, depending on the degree of change.3 ΔmRS score also directly correlated with increasing social and health care costs. ΔmRS score ≥2 was associated with a $40 533 (95% CI, $8,827–72,240; P=0.012) increased cost over 5 years. This highlights the high societal costs of routinely withholding acute stroke treatments in patients with prestroke disability, as well as the potential opportunities for care and mitigation of further disability with therapies such as thrombolysis and EVT in these patients.
Current Evidence for the Safety and Efficacy of Thrombolysis and EVT in Patients With Prestroke Disability or Dementia
Current evidence on thrombolysis (Table 1) and EVT (Table 2) in patients with prestroke disability or dementia is mostly from observational studies, namely case-control studies and some registries. These studies are subject to significant selection bias; a smaller proportion of patients with prestroke dementia or disability receive intervention than individuals without prestroke dementia or disability. Studies comparing outcomes for patients with premorbid disability/dementia treated with thrombolysis or EVT and patients with disability/dementia who are managed medically are scarce, as are randomized trials for populations with prestroke disability or dementia. The only major EVT trial that permitted the enrollment of patients with prestroke disability was MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), which included 45 patients with a prestroke mRS score ≥2 (of whom 26 had an mRS score of 2), but these patients were not analyzed separately.54 Variable thresholds for the definition of disability further hamper efforts at direct comparison between studies.
| Author and year published | Study design | Patient population | Study intervention, n patients/study comparator, n patients | Poststroke disability outcomes | Mortality outcomes | ICH, sICH, and other safety outcomes | Other comments |
|---|---|---|---|---|---|---|---|
| Caruso et al,41 2020 | Retrospective, single center, 2015–2017, n=35 | AIS treated with IVT (3 also EVT), prestroke mRS score ≥2 | 12 prestroke mRS score 2, 14 prestroke mRS score 3, 9 prestroke mRS score 4–5, 247 AIS-IVT with prestroke mRS score <2 | Treated subjects with mRS score <2 showed lower mRS score at discharge (median, 1; range, 0–6) and similar ΔNIHSS score (−75%). | Mortality (unclear time point) 2/12 (17%) prestroke mRS score 2, 3/14 (21.4%) mRS score 3, 4/9 (44%) mRS score 4–5 vs 4.7% for mRS score <2 | sICH in 3/12 (22%) mRS score 2, 2/14 (14%) mRS score 3, 2/9 (22%) mRS score 4–5 vs 5 with mRS score <2 | In surviving patients, median percent change in NIHSS score was higher in the mRS score 2 and 3 groups (−63.3% and −92.3%, respectively) than in the mRS score 4–5 group (−9.1%) |
| Merlino et al,42 2019 | Retrospective, single center, 2015–2018, n=110 | AIS, IVT eligible, prestroke mRS score 3–4, thrombectomy excluded | 36 treated with IVT, 74 with no IVT | Favorable outcome=3-mo return to prestroke mRS score associated with IVT vs no IVT; OR, 3.5 (95% CI, 1.4–8.9) | Similar 3-mo mortality (OR, 1.2 [95% CI, 0.4–3.3]) | Similar rates of ICH (OR, 2.2 [95% CI, 0.4–12.4]) and sICH (2 vs 0; P=0.10) | Neurological improvement, ie ≥8-point NIHSS score improvement or NIHSS score 0 at discharge (OR, 2.9 [95% CI, 1.0-8.0]) |
| Gumbinger et al,43 2019 | German statewide registry 2008–2014, n=52 741 | AIS presenting within 4.5 h; 23.5% with prestroke disabilities (mRS score >0) | 29% of total treated with IVT, inversely correlated with prestroke mRS score (eg, 32.9% mRS score 0 vs 20.2% mRS score 3, 11.2% mRS score 5) | Favorable outcome at discharge (mRS score 0–1 or return to prestroke mRS score) independently associated with IVT for all prestroke mRS score 0–4; multivariable aOR, 1.73 (95% CI, 1.61–1.86) mRS score 0 vs 1.57 (95% CI, 1.24–1.99) mRS 3 and 1.60 (95% CO. 1.13–2.27) mRS score 4 | Morality at discharge not independently associated with IVT for any of the prestroke mRS score >0 groups | Not reported in this article | |
| Zhang et al,44 2018 | Retrospective, single-center 2005–2016, n=820 consecutive patients | AIS treated with IVT | 680 premorbid mRS score 0–1, 140 mRS score 2–4 | Return to premorbid mRS score at 90 d in 24.9%, 38.3%, 32.3%, 29.7%, and 25.0% of patients with premorbid mRS scores 0, 1, 2, 3, and 4, respectively (nonsignificant) | Preexisting disability associated with increased mortality (35.7% vs 12.8%; P<0.05) | sICH across same categories 3.3%, 7.4%, 40%, 13.5%, 25% (nonsignificant) | 60% of those with premorbid mRS score 3 and 74.8% with premorbid mRS score 4 were eligible but excluded from alteplase; treated patients with premorbid disability had longer onset-to-needle time |
| Zupanic 201731 | Swedish Dementia Registry 2007–2014 with strokes identified by Riksstroke national stroke registry, nested case-control | AIS, restricted to 2010–2014 when 4.5-h IVT window was instituted | 1356 patients with dementia with AIS vs 6755 dementia-free control subjects matched by age, sex, stroke year, and geographic region | Increased 3-mo mRS score for prestroke dementia (OR for ordinal logistic regression, 3.65 [95% CI, 2.06–6.45]) and new nursing home placement (4.39 [95% CI, 2.07–9.31]) | No difference in 3-mo mortality (OR for dementia vs no dementia, 0.71 [95% CI, 0.36–1.8]) | No difference in sICH (7.4% vs 7.3%) | Prestroke dementia associated with lower likelihood of IVT (7% vs 9.5%; aOR, 0.68 [95% CI, 0.54–0.86]; similar results with propensity matching) |
| Gensicke et al,32 2016 | Prospective registry study, n=7430 | Consecutive AIS treated with IVT | 6941 prestroke mRS score 0–2 vs 489 prestroke mRS score 3–5 | No difference for 3-mo poor outcome (defined as mRS score 3–6 if prestroke score ≤2, increased poststroke mRS score if prestroke mRS score >2; aOR, 0.95 (95% CI, 0.75–1.21) | 3-mo mortality increased with prestroke disability (OR, 2.19 [95% CI, 1.70–2.84]; P<0.001) | sICH occurred equally frequently in those with and those without disability (4.8% vs 4.5%) | Among survivors and after adjustment for age and NIHSS score, lower likelihood for poor outcome among prestroke mRS score >2 (aOR, 0.64 [95% CI, 0.49–0.84]; P=0.001) |
| Karlinski et al,38 2014 | SITS-EAST prospective registry 2003–2011, n=7250 | Consecutive AIS treated with IVT | 171 prestroke mRS score 3–5, 293 prestroke mRS score 2, 790 prestroke mRS score 1, 5990 prestroke mRS score 0 | For favorable 3-mo outcome (mRS score 0–2 or return to prestroke mRS score), aOR, 0.80 (95% CI, 0.65–1.0), 0.41 (95% CI, 0.28–0.60), 0.59 (95% CI, 0.34–1.01) | Prestroke mRS scores 1, 2, and ≥3 associated with increased risk of death at 3 mo (OR, 1.3, 2.0, and 2.6) Patients with prestroke mRS score ≥3 had higher mortality than those with mRS score 2 (48% vs 39%) | Multivariable aORs (95% CIs) across mRS scores 1, 2, and 3–5 relative to mRS score 0 for sICH: 1.36 (0.99–1.86), 1.12 (0.67–1.88), 1.18 (0.58–2.43) Sensitivity analysis excluding patients with prior stroke showed increased sICH with mRS score 3–5 | For NIHSS score ≥4-point improvement day 7, multivariable aORs (95% CIs) across prestroke mRS scores 1, 2, and 3–5 vs mRS score 0: 1.0 (0.85–1.18), 0.64 (0.49–0.85), 0.59 (0.38–0.90) |
| Busl et al,37 2013 | Retrospective, single center, 2002–2009, n=153 (110 IVT, 54 IAT, 11 both) | AIS treated with IVT or IAT, age >80 y | 21 prestroke dementia vs 132 no prestroke dementia | Favorable discharge (home or acute rehabilitation) 7/21 (33.3%) vs 76/132 (57.6%; OR, 0.37 [95% CI, 0.12–1.06]; P=0.38) | In-hospital mortality, 13/21 (61.9%) vs 41/132 (31.1%; OR, 3.6 [95% CI, 1.4–9.4]; P=0.01) | sICH 3/21 (14.2%) with prestroke dementia, 7/132 (5.3%; OR, 3.0 [95% CI, 0.5–14.4]; P=0.14) no dementia | |
| Saposnik et al,35 2012 | Canadian Stroke Network registry 2003–2008, retrospective analysis, n=10 658 and nested case-control | AIS treated with and without IVT | Total registry: 966 prestroke dementia, 9692 no dementia Nested case-control: 877 with dementia, 877 without, propensity matched by age, sex, severity, type, comorbidities, and treatment characteristics | Disability at discharge similar between patients with dementia and those without in the matched sample (85.2% vs 82.7%); slight increase in disability (RR, 1.10 [95% CI, 1.02–1.19]) when only patients discharged alive were included | In full cohort, no difference in 30-d mortality with vs without dementia (RR, 0.96 [95% CI, 0.81–1.12]); in matched analysis, no difference in 30-d mortality (RR, 0.88 [95% CI, 0.75–1.03]) | No significant difference in sICH (RR, 1.28 [95% CI, 0.63–2.60]) | Patients with dementia less likely to receive IVT (10.5% vs 16.2%) |
| Alshekhlee et al,45 2011 | Retrospective, US National Inpatient Sample database 2000–2007, nested case-control | AIS treated with IVT | 207 treated patients with dementia, 621 without dementia probability matched for age, sex, and race | NA | No difference between patients with and those without dementia in rate of death (17.4% vs 14.5%) | No difference in ICH (5.8% with dementia vs 4.5% without) | Proportion receiving thrombolysis 0.58% for patients with dementia vs 1.28% in full sample |
| Foell et al,46 2003 | Prospective observational study, n=112 | Consecutive AIS treated with IVT | 24 prestroke mRS score ≥2 vs 88 prestroke mRS score ≤1 | Median mRS score 3 with premorbid disability vs 2 without. No difference in favorable outcome defined as mRS score 0–1 or return to pre-stroke mRS score (41% vs 42%) | 3-mo mortality, 33% vs 14% | 2 sICH in those with disability (8.3%) vs 1 without (1.1%), all fatal, no significant difference |
Studies are presented in reverse chronological order.
AIS indicates acute ischemic stroke; aOR, adjusted odds ratio; IAT, intra-arterial reperfusion therapy; IVT, intravenous thrombolysis; mRS, modified Rankin Scale; NA, not applicable; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; RR, relative risk; sICH, symptomatic intracerebral hemorrhage; and SITS-EAST, Safe Implementation of Treatments in Stroke–East.
| Author and year published | Study design | Patient population | Study intervention, n patients/study comparator, n patients | Poststroke disability outcomes | Mortality outcomes | ICH, sICH, or other safety outcomes | Other comments |
|---|---|---|---|---|---|---|---|
| Salwi, et al47 2020 | Retrospective, dual center, 2012–2018, n=761 | Consecutive patients with AIS treated with EVT | 259 patients with moderate prestroke disability mRS score ≥2 vs 502 prestroke mRS score ≤1 | 90-d mRS score ≤1 or unchanged from baseline disability in 36.7% vs 26.7% (aOR, 0.90 [95% CI, 0.60–1.35]; P=0.6) | 90-d mortality higher with prestroke mRS score ≥2 (aOR, 2.83 [95% CI, 1.84-4.37]; P<0.001) | No differences between groups in sICH | Two-thirds of thrombectomy population had baseline mRS score ≥2; no differences in reperfusion, length of stay by prestroke mRS score |
| Regenhardt et al,48 2020 | Retrospective, single center, 2011–2019, n=381 | Consecutive patients with AIS treated with EVT | 49 patients with baseline disability (5 mRS score 4, 23 mRS score 3, 21 mRS score 2), 332 without | Baseline disability associated with 90-d mRS score ≤2 (OR, 0.51 [95% CI, 0.37–0.70]) but not accumulated disability by ∆mRS score ≤0 | Higher 90-d mortality in those with prestroke disability (50% vs 19%; P<0.0001) | No differences in complications, including ICH (OR, 0.52 [95% CI, 0.24-1.11]) | No association between baseline disability and accumulated disability or other thrombectomy outcomes |
| Salwi 202049 | Retrospective, dual center, 2012–2018, n=855 | Selected patients with severe baseline disability (mRS score 4 or 5) | 33 patients (4% of total) identified from 822 patients total | 36% return to baseline functional status comparable to historical data on patients without premorbid disability | 8 patients (24.2%) died in hospital | 6.2% had sICH | Rate of 84% successful recanalization; small numbers of patients without direct comparator group; selection bias |
| Larsson et al,50 2020 | Retrospective, single center, 2015–2018, n=591 | Consecutive patients with AIS treated with EVT | 90 patients with baseline disability mRS score ≥3 vs 501 with mRS score ≤2 | Recanalization rates and return to prestroke functional baseline were similar between groups; 20% with prestroke disability returned to baseline | Mortality at 90 d higher in patients with prestroke disability | sICH similar between groups | |
| Oesch et al,51 2020 | Prospective, observational registry study, multicenter, 2005–2016, n=1247 | Consecutive patients with AIS treated with EVT | 84 patients with prestroke mRS score ≥3 vs 1163 with prestroke mRS score ≤2 | Preexisting disability not associated with clinical outcome (aOR, 1.08 [95% CI, 0.61–1.89]) | Preexisting disability not associated with mortality (aOR, 1.27 [95% CI, 0.76–2.1]) | sICH similar in both groups | Significant baseline differences besides disability (age, history of stroke, presence of vascular risk factors, baseline NIHSS score) |
| Leker et al,52 2019 | Prospective, observational registry study, multicenter, 2017–2018, n=390 | Consecutive patients with AIS treated with EVT | 35 patients with previous stroke, 355 patients without previous stroke | Return to previous disability level in 9% with previous stroke | Higher 1-y mortality with prior stroke (37% vs 16%; P=0.005) | sICH similar between groups | Patients with prior strokes had higher prestroke disability (48% vs 13%; P<0.001) and lower reperfusion rates (60% vs 82%; P=0.005) |
| Slawski et al,33 2018 | Retrospective, single center, 2015–2017, n=96 | Consecutive patients >80 y of age treated with EVT | 46 patients with moderate prestroke disability mRS score 2–4 vs 50 prestroke mRS score ≤1 | No significant differences in return to baseline disability between mild and moderate baseline disability groups (43% vs 24%; P=0.08) | Mortality rate, 38.5% at 90 d; higher with prior disability vs without (52.2% vs 26%; P=0.012) | No significant difference in sICH in those with vs those without premorbid disability (8.7% vs 4%; P=0.42) | No association of outcome in either group with very elderly (>85 y) or time >8 h from onset |
| Goldhoorn et al,53 2018 | Prospective, observational registry study, multicenter, 2014–2016, n=1441 | Consecutive patients with anterior circulation occlusions treated with EVT | 157 patients with moderate prestroke disability mRS score 3–5 vs 1284 patients with prestroke mRS score ≤2 | Return to baseline disability in 27% of disabled patients vs 42% prestroke independent patients (aOR, 0.90 [95% CI, 0.58–1.39]) | Higher mortality at 90 d with prestroke disability (aOR, 2.07 [95% CI, 1.40–3.04]) | sICH and stroke progression similar between groups | Large sample, representative of clinical practice; 11% of registry population had prestroke disability |
Studies are presented in reverse chronological order.
AIS indicates acute ischemic stroke; aOR, adjusted odds ratio; EVT, endovascular therapy; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; RR, risk ratio; and sICH, symptomatic intracerebral hemorrhage.
These limitations notwithstanding, there is no consistent evidence at present to support the concern that prestroke dementia or disability may be associated with increased risk of symptomatic intracerebral hemorrhage associated with reperfusion therapies (Tables 1 and 2). There is a paucity of data comparing treated patients with prestroke disability/dementia with untreated patients (versus patients without prestroke disability/dementia); there is also no convincing evidence for a loss of treatment benefit with reperfusion therapies in these populations. There is some (albeit inconsistent) evidence for increased mortality and reduced return to prestroke function after thrombolysis of patients with prestroke dementia/disability. On the other hand, for EVT, the rates of accumulated poststroke disability (versus return to prestroke function) appear similar for patients with prestroke disability compared with those without prestroke disability.
Ethics of Inclusion Versus Exclusion of Patients With Disability or Dementia From Treatment
When considering the question of providing or withholding acute stroke therapies for patients with prestroke disability or dementia, we must also consider the various ethical dimensions involved. These are discussed further in the Supplemental Material. Briefly, in the absence of definitive evidence on the balance of risks versus benefits of therapy, it is challenging to base treatment decisions only on the ethical pillars of beneficence and nonmaleficence. Under such circumstances, stroke teams should, whenever possible, seek to respect a patient’s autonomy or their wishes and values as expressed by their proxies in the acute stroke setting. Basing decisions on a perceived lack of cost-effectiveness or futile resource use is difficult to justify in the absence of high-quality effectiveness or cost data in this patient population. On the other hand, enthusiasm to treat these patients must be tempered by the reality that individuals with multiple comorbidities and disability are more likely to succumb to complications of acute stroke. Providing good end-of-life palliative care to patients with stroke and their families is an inherent moral obligation of the stroke community. This aspect needs to be weighed in discussions of acute treatment allocation and its merits. Furthermore, several biases can influence a physician’s or caregiver’s decision-making process when considering the use of acute stroke therapies in patients with premorbid disability or dementia. These include ableism, impact or ineffectual bias, optimism bias, fragility bias, catastrophe bias, therapeutic nihilism, medical paternalism, and biases from lived experience (or lack thereof), which are discussed further in Supplemental Table 2. Being cognizant of these biases can help physicians think critically about their decision-making and better cater to patient-centered ethical principles.
Considerations for the Use of Acute Stroke Therapies in Patients With Premorbid Disability or Dementia in Routine Practice
Given the limitations of existing data and the many nuances involved in the care of patients with premorbid disability or dementia, as discussed above, it is difficult to draw any firm recommendations about the use of acute stroke therapies such as thrombolysis or EVT in this patient population at this time. However, from the best available literature, it seems reasonable to conclude that a blanket disability cutoff such as a premorbid mRS score of 2 probably should not be used as a protocolized threshold to exclude patients from acute stroke therapies. Instead, we may consider a pragmatic, case-by-case approach to the use of acute stroke therapies in patients with premorbid disability or dementia, pending the availability of more definitive evidence (Figure 1). Key elements of this approach include acknowledging the spectrum of good and bad outcomes that may be achieved in these patients, disclosing the uncertain state of the evidence when discussing treatment options with patients or proxies, and adopting patient-centered care strategies whenever possible, taking into account their long-term goals of care. Such discussions should acknowledge the potential added risks involved in treating these patients, given that observational studies have fairly consistently shown higher mortality among treated patients with premorbid disability/dementia compared with those without disability/dementia (the limitations of such comparisons as noted above notwithstanding). Treatment risks will also be modified by additional patient-specific data; for example, patients with prestroke disability/dementia may have previous neuroimaging showing a considerable burden of white matter hyperintensities or microbleeds, known to increase the risk of postthrombolysis intracerebral hemorrhage.55,56
This approach also recognizes that the patient’s outcome will depend not just on the immediate treatment decision at hand but also on a continuing high quality of postacute care. Indeed, there is also growing evidence for the importance of such postacute care, including rehabilitation and stroke unit care, to prevent complications such as pneumonia, which may erode any benefits of thrombolysis or EVT even among premorbidly healthy patients.57 Ensuring access to assistive technologies and psychosocial supports also may help these patients better adapt to life after stroke despite their greater disability. At present, access to such supports is often dependent on the patients’ socioeconomic and health insurance status and varies considerably from state to state within the United States.58,59
Outside the acute stroke setting such as in the stroke prevention or neurovascular clinic, physicians should discuss quality-of-life concerns and future care preferences with patients at risk of major stroke who have preexisting disability or dementia, including their caregivers or families as appropriate. Such discussions can facilitate advanced care planning, including living wills or advanced care directives noting patient preferences for acute stroke care, the practical limitations of such advance decisions in influencing eventual care pathways notwithstanding.60 Health care systems should invest greater resources in the accurate documentation of the wishes and values of patients with disability or dementia and in ensuring that such documentation is readily available for health care teams during emergency situations, without relying on the availability of family members or caregivers. In this regard, health care systems should foster a culture in which issues related to quality of life and patients’ wishes or values are openly discussed, documented, and shared in a standardized format.
Roadmap for Future Studies of Acute Stroke Therapies in Patients With Prestroke Disability or Dementia
As our societies age, the patient population with acute stroke can be expected to increasingly comprise older patients with multiple comorbidities, disability, or dementia.61 The stroke community has an obligation to generate higher-quality data to inform stroke care in this expanding population. Several important factors must be addressed to improve the state of stroke research with regard to patients with prestroke disability or dementia (Figure 2). The ascertainment and measurement of premorbid disability or dementia in the setting of acute stroke continue to be a challenge. If we are to conduct high-quality randomized controlled trials including patients with premorbid disability, we need harmonized, validated strategies to measure disability and capture these data. We also need to develop better measures that not only are reliable in an acute stroke setting but also help elucidate the nature of a given patient’s disability (eg, cognitive versus physical), currently not well captured by the mRS. Ideally, such premorbid measures also should be captured in clinical registries. Such registries could additionally capture the causes of or contributors to prestroke disability in each patient because outcomes likely differ by disability pathogenesis. For example, disability from prior strokes versus from orthopedic causes may have different implications, but such comparisons are missing in the literature.
In addition, 3-month mRS score dichotomies of 0 to 1/2 to 6 or 0 to 2/3 to 6 fail to capture the potential benefits of treatment in patients with a mix of different levels of prestroke disability. To promote greater inclusion of patients with prestroke disability, it is time for acute stroke trials to move away from these conventional dichotomies. Instead, ordinal mRS approaches, including measures like the ΔmRS score (capturing the change in mRS score from before to after stroke), or more inclusive dichotomous outcomes such as return to prestroke mRS score or avoidance of the devastating outcome of an mRS score of 5 to 6 should be strongly considered, being far more reflective of long-term outcomes.3,62 Other measures such as home time (time spent at home after stroke),63 health care costs, and quality of life also would be valuable in this population, at least as secondary outcomes, to facilitate much-needed cost-effectiveness analyses.
There is also a need for high-quality mixed-methods studies involving physicians, patients, and caregivers to better inform current policies and the design of future trials in this population. The current literature tells us little about how physicians actually deal with the uncertainty of present evidence, that is, how they balance the uncertain benefits and risks of therapy when caring for patients with prestroke disability/dementia. Whereas there is a growing body of literature from observational studies (mostly treatment registries), these studies do not help us understand why the patients with prestroke disability/dementia captured in these studies were treated and, perhaps more important, how many others were not treated, why they were not treated, and how those untreated patients fared.
Our failure to engage such patients in research on poststroke recovery and adaptation is unfortunate because we end up excluding the very patients carrying the greatest burden of illness.64 If we do not actively incorporate these voices, then the dialog on acute stroke therapies becomes restricted to doctors and policy makers, incurring the risks of group think65 and failing to empower the autonomy of patients with disability or dementia and their caregivers. Therefore, we also need to engage these patients and their families/caregivers to capture their views and experiences in relation to (1) the uncertain benefits (versus risks) of acute stroke therapies, (2) potentially living a longer life with greater disability after stroke, and (3) involvement in acute stroke trials. This type of work would ideally include qualitative/mixed-methods studies on patients’ wishes and expectations about stroke care, with emphasis on capturing diverse perspectives (different age groups, ethnicities, physical and cognitive disabilities, etc). The field could also benefit from the reflections and quantitative follow-up assessments (eg, quality of life) of patients with premorbid disability/dementia who received acute stroke therapies (versus those who did not) and their caregivers. Such data can help us understand their perspectives and satisfaction with their acute treatment decisions; similar data have meaningfully informed discussions about decompressive craniectomy in acute stroke.66 Equity, diversity, and inclusion initiatives in stroke research should also promote training and leadership opportunities for physicians living with disability, so that people with disability are represented among the investigators themselves.
As an initial step toward better efficacy data in this population, we encourage the systematic measurement and tracking of prestroke versus poststroke functional outcome in patients with prestroke disability and dementia in prospective registries of acute stroke. Ideally, these registries should capture data on both treated and untreated patients (the latter generally missing from existing data), so that posttreatment outcomes in patients with prestroke disability/dementia may be compared with those of untreated patients of similar prestroke status, instead of expecting them to meet the arbitrary standard of treated patients without disability/dementia. We also encourage the enrollment of patients with prestroke disability/dementia in phase 4 trials of thrombolysis/EVT and in future trials of new therapies. Studies enrolling such mixed populations should plan for separate subgroup analyses of patients with physical and cognitive disability. Given the potential limitations added to the informed consent process in this patient population (particularly those with intellectual/cognitive disability or dementia), consideration may be given to strategies such as caregiver/proxy assent or, if appropriate, waiver of consent to facilitate the inclusion of these patients.67 Incorporating telephone- or video-assisted remote follow-up visits can also empower such patients to participate in stroke trials. Research and development into better assistive and rehabilitative technologies also will help improve poststroke outcomes in these patients. Our recommendations for future research are summarized in Supplemental Table 3.
Conclusions
The absence of definitive evidence on the efficacy of thrombolysis and EVT in patients with premorbid disability or dementia results in difficult decisions about the use of these therapies. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of prestroke disability or prestroke dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies also have helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have provided safety data on EVT and thrombolysis in patients with premorbid disability/dementia. These data are complicated because, on the one hand, they demonstrate similar hemorrhagic risks in treated patients with premorbid disability/dementia compared with treated patients without disability/dementia, but on the other hand, they have found much higher mortality in the former group. These observational data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.
Supplemental Material
References
1.
Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, et al; on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics–2021 update: a report from the American Heart Association. Circulation. 2021;143:e254–e743. doi: 10.1161/CIR.0000000000000950
2.
World Health Organization. World Report on Disability. World Health Organization; 2011. Accessed November 25, 2021. https://www.who.int/disabilities/world_report/2011/report.pdf
3.
Ganesh A, Luengo-Fernandez R, Pendlebury ST, Rothwell PM. Long-term consequences of worsened poststroke status in patients with premorbid disability. Stroke. 2018;49:2430–2436. doi: 10.1161/STROKEAHA.118.022416
4.
Pendlebury ST, Rothwell PM; Oxford Vascular Study. Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular Study. Lancet Neurol. 2019;18:248–258. doi: 10.1016/S1474-4422(18)30442-3
5.
IST-3 Collaborative Group. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurol. 2013;12:768–76. doi: 10.1016/S1474-4422(13)70130-3
6.
Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Dávalos A, Majoie CB, van der Lugt A, de Miquel MA, et al; HERMES Collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387:1723–1731. doi: 10.1016/S0140-6736(16)00163-X
7.
Paciaroni M, Pantoni L. Thrombolysis in dementia patients with acute stroke: is it justified? Neurol Sci. 2017;38:27–31. doi: 10.1007/s10072-016-2725-4
8.
Cappellari M, Bosco M, Forlivesi S, Tomelleri G, Micheletti N, Carletti M, Bovi P. Reasons for exclusion from intravenous thrombolysis in stroke patients admitted to the stroke unit. J Thromb Thrombolysis. 2016;42:593–599. doi: 10.1007/s11239-016-1406-8
9.
Saposnik G, Cote R, Rochon PA, Mamdani M, Liu Y, Raptis S, Kapral MK, Black SE; Registry of the Canadian Stroke Network; Stroke Outcome Research Canada (SORCan) Working Group. Care and outcomes in patients with ischemic stroke with and without preexisting dementia. Neurology. 2011;77:1664–1673. doi: 10.1212/WNL.0b013e31823648f1
10.
Fiehler J, Cognard C, Gallitelli M, Jansen O, Kobayashi A, Mattle HP, Muir KW, Mazighi M, Schaller K, Schellinger PD. European recommendations on organisation of interventional care in acute stroke (EROICAS). Int J Stroke. 2016;11:701–716. doi: 10.1177/1747493016647735
11.
Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, Schellinger PD, Toni D, de Vries J, White P, et al. European Stroke Organisation (ESO)- European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischemic stroke. J Neurointerv Surg. 2019;11:535–538. doi: 10.1136/neurintsurg-2018-014568
12.
Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, Khalessi AA, Levy EI, Palesch YY, Prabhakaran S, et al; on behalf of the American Heart Association Stroke Council and Council on Epidemiology and Prevention. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association [published correction appears in Stroke. 2016;47:e262]. Stroke. 2016;47:581–641. doi: 10.1161/STR.0000000000000086
13.
Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, et al; on behalf of the American Heart Association Stroke Council. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [published correction appears in Stroke. 2018;49:e138 and Stroke. 2018;49:e233–e234]. Stroke. 2018;49:e46–e110. doi: 10.1161/STR.0000000000000158
14.
De Haan R, Horn J, Limburg M, Van Der Meulen J, Bossuyt P. A comparison of five stroke scales with measures of disability, handicap, and quality of life. Stroke. 1993;24:1178–1181. doi: 10.1161/01.str.24.8.1178
15.
Wolfe CD, Taub NA, Woodrow EJ, Burney PG. Assessment of scales of disability and handicap for stroke patients. Stroke. 1991;22:1242–1244. doi: 10.1161/01.str.22.10.1242
16.
Wood, P. International Classification of Impairments, Disabilities and Handicaps: A Manual of Classification Relating to the Consequences of Disease. World Health Organization; 1980.
17.
American Psychiatric Association. Major and mild neurocognitive disorders. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th ed. APA Publishing; 2013: 602.
18.
Ganesh A, Ospel JM, Kromm J, Goyal M. Ignorance is not bliss: managing uncertainty in acute stroke treatment in the COVID-19 era. Neuroradiology. 2021;63:3–6. doi: 10.1007/s00234-020-02592-9
19.
Lees KR, Bath PM, Schellinger PD, Kerr DM, Fulton R, Hacke W, Matchar D, Sehra R, Toni D; European Stroke Organization Outcomes Working Group. Contemporary outcome measures in acute stroke research: choice of primary outcome measure. Stroke. 2012;43:1163–1170. doi: 10.1161/STROKEAHA.111.641423
20.
McArthur K, Beagan ML, Degnan A, Howarth RC, Mitchell KA, McQuaige FB, Shannon MA, Stott DJ, Quinn TJ. Properties of proxy-derived modified Rankin Scale assessment. Int J Stroke. 2013;8:403–407. doi: 10.1111/j.1747-4949.2011.00759.x
21.
Quinn TJ, Ray G, Atula S, Walters MR, Dawson J, Lees KR. Deriving modified Rankin scores from medical case-records. Stroke. 2008;39:3421–3423. doi: 10.1161/STROKEAHA.108.519306
22.
Labovitz DL. Stroke epidemiology and intersectionality: understanding stroke outcomes in Mexican Americans in Corpus Christi. Stroke. 2020;51:2886–2887. doi: 10.1161/STROKEAHA.120.031848
23.
Renoux C, Coulombe J, Li L, Ganesh A, Silver L, Rothwell PM; Oxford Vascular Study. Confounding by pre-morbid functional status in studies of apparent sex differences in severity and outcome of stroke. Stroke. 2017;48:2731–2738. doi: 10.1161/STROKEAHA.117.018187
24.
Carcel C, Wang X, Sandset EC, Delcourt C, Arima H, Lindley R, Hackett ML, Lavados P, Robinson TG, Muñoz Venturelli P, et al. Sex differences in treatment and outcome after stroke: pooled analysis including 19,000 participants. Neurology. 2019;93:e2170–e2180. doi: 10.1212/WNL.0000000000008615
25.
IST Collaborative Group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, Innes K, Venables G, Czlonkowska A, Kobayashi A, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third International Stroke Trial [IST-3]): a randomised controlled trial. Lancet. 2012;379:2352–2363. doi: 10.1016/S0140-6736(12)60768-5
26.
Power MC, Bennett EE, Turner RW, Dowling NM, Ciarleglio A, Glymour MM, Gianattasio KZ. Trends in relative incidence and prevalence of dementia across non-Hispanic Black and White individuals in the United States, 2000-2016. JAMA Neurol. 2021;78:275–284. doi: 10.1001/jamaneurol.2020.4471
27.
Mehta KM, Yeo GW. Systematic review of dementia prevalence and incidence in United States race/ethnic populations. Alzheimers Dement. 2017;13:72–83. doi: 10.1016/j.jalz.2016.06.2360
28.
Innocenti E, Nencini P, Romani I, Del Bene A, Arba F, Piccardi B, Pracucci G. Delay in presentation after acute ischemic stroke: the Careggi Hospital Stroke Registry. Neurol Sci. 2014;35:49–52. doi: 10.1007/s10072-013-1484-8
29.
Fladt J, Meier N, Thilemann S, Polymeris A, Traenka C, Seiffge DJ, Sutter R, Peters N, Gensicke H, Flückiger B, et al. Reasons for prehospital delay in acute ischemic stroke. J Am Heart Assoc. 2019;8:e013101. doi: 10.1161/JAHA.119.013101
30.
Zupanic E, Kåreholt I, Norrving B, Secnik J, von Euler M, Winblad B, Religa D, Kramberger MG, Johnell K, Eriksdotter M, et al. acute stroke care in dementia: a cohort study from the Swedish dementia and stroke registries. J Alzheimers Dis. 2018;66:185–194. doi: 10.3233/JAD-180653
31.
Zupanic E, von Euler M, Kåreholt I, Contreras Escamez B, Fastbom J, Norrving B, Religa D, Kramberger MG, Winblad B, Johnell K, et al. Thrombolysis in acute ischemic stroke in patients with dementia: a Swedish registry study. Neurology. 2017;89:1860–1868. doi: 10.1212/WNL.0000000000004598
32.
Gensicke H, Strbian D, Zinkstok SM, Scheitz JF, Bill O, Hametner C, Moulin S, Zini A, Kägi G, Pezzini A, et al; Thrombolysis in Stroke Patients (TriSP) Collaborators. Intravenous thrombolysis in patients dependent on the daily help of others before stroke. Stroke. 2016;47:450–456. doi: 10.1161/STROKEAHA.115.011674
33.
Slawski DE, Salahuddin H, Shawver J, Kenmuir CL, Tietjen GE, Korsnack A, Zaidi SF, Jumaa MA. Mechanical thrombectomy in elderly stroke patients with mild-to-moderate baseline disability. Interv Neurol. 2018;7:246–255. doi: 10.1159/000487333
34.
Callisaya ML, Purvis T, Lawler K, Brodtmann A, Cadilhac DA, Kilkenny MF. Dementia is associated with poorer quality of care and outcomes after stroke: an observational study. J Gerontol A Biol Sci Med Sci. 2021;76:851–858. doi: 10.1093/gerona/glaa139
35.
Saposnik G, Kapral MK, Cote R, Rochon PA, Wang J, Raptis S, Mamdani M, Black SE. Is pre-existing dementia an independent predictor of outcome after stroke? A propensity score-matched analysis. J Neurol. 2012;259:2366–2375. doi: 10.1007/s00415-012-6508-4
36.
Han TS, Fry CH, Gulli G, Affley B, Robin J, Irvin-Sellers M, Fluck D, Kakar P, Sharma S, Sharma P. Prestroke disability predicts adverse poststroke outcome: a registry-based prospective cohort study of acute stroke. Stroke. 2020;51:594–600. doi: 10.1161/STROKEAHA.119.027740
37.
Busl KM, Nogueira RG, Yoo AJ, Hirsch JA, Schwamm LH, Rost NS. Prestroke dementia is associated with poor outcomes after reperfusion therapy among elderly stroke patients. J Stroke Cerebrovasc Dis. 2013;22:718–724. doi: 10.1016/j.jstrokecerebrovasdis.2011.11.005
38.
Karlinski M, Kobayashi A, Czlonkowska A, Mikulik R, Vaclavik D, Brozman M, Svigelj V, Csiba L, Fekete K, Kõrv J, et al; Safe Implementation of Treatments in Stroke–Eastern Europe (SITS-EAST) Investigators. Role of preexisting disability in patients treated with intravenous thrombolysis for ischemic stroke. Stroke. 2014;45:770–775. doi: 10.1161/STROKEAHA.113.003744
39.
Subic A, Cermakova P, Norrving B, Winblad B, von Euler M, Kramberger MG, Eriksdotter M, Garcia-Ptacek S. Management of acute ischaemic stroke in patients with dementia. J Intern Med. 2017;281:348–364. doi: 10.1111/joim.12588
40.
Garcia-Ptacek S, Contreras Escamez B, Zupanic E, Religa D, von Koch L, Johnell K, von Euler M, Kåreholt I, Eriksdotter M. Prestroke mobility and dementia as predictors of stroke outcomes in patients over 65 years of age: a cohort study from the Swedish dementia and stroke registries. J Am Med Dir Assoc. 2018;19:154–161. doi: 10.1016/j.jamda.2017.08.014
41.
Caruso P, Ajčević M, Furlanis G, Ridolfi M, Lugnan C, Cillotto T, Naccarato M, Manganotti P. Thrombolysis safety and effectiveness in acute ischemic stroke patients with pre-morbid disability. J Clin Neurosci. 2020;72:180–184. doi: 10.1016/j.jocn.2019.11.047
42.
Merlino G, Corazza E, Lorenzut S, Gigli GL, Cargnelutti D, Valente M. Efficacy and safety of intravenous thrombolysis in patients with acute ischemic stroke and pre-existing disability. J Clin Med. 2019;8:400. doi: 10.3390/jcm8030400
43.
Gumbinger C, Ringleb P, Ippen F, Ungerer M, Reuter B, Bruder I, Daffertshofer M, Stock C; Stroke Working Group of Baden-Württemberg. Outcomes of patients with stroke treated with thrombolysis according to prestroke Rankin Scale scores. Neurology. 2019;93:e1834–e1843. doi: 10.1212/WNL.0000000000008468
44.
Zhang W, Coote S, Frost T, Dewey HM, Choi PMC. Acute stroke patients with mild-to-moderate pre-existing disability should be considered for thrombolysis treatment. J Stroke Cerebrovasc Dis. 2018;27:2707–2711. doi: 10.1016/j.jstrokecerebrovasdis.2018.05.051
45.
Alshekhlee A, Li CC, Chuang SY, Vora N, Edgell RC, Kitchener JM, Kale SP, Feen E, Piriyawat P, Callison RC, et al. Does dementia increase risk of thrombolysis? A case-control study. Neurology. 2011;76:1575–1580. doi: 10.1212/WNL.0b013e3182190d37
46.
Foell RB, Silver B, Merino JG, Wong EH, Demaerschalk BM, Poncha F, Tamayo A, Hachinski V. Effects of thrombolysis for acute stroke in patients with pre-existing disability. CMAJ. 2003;169:193–197.
47.
Salwi S, Cutting S, Salgado AD, Espaillat K, Fusco MR, Froehler MT, Chitale RV, Kirshner H, Schrag M, Jasne A, et al. Mechanical thrombectomy in patients with ischemic stroke with prestroke disability. Stroke. 2020;51:1539–1545. doi: 10.1161/STROKEAHA.119.028246
48.
Regenhardt RW, Young MJ, Etherton MR, Das AS, Stapleton CJ, Patel AB, Lev MH, Hirsch JA, Rost NS, Leslie-Mazwi TM. Toward a more inclusive paradigm: thrombectomy for stroke patients with pre-existing disabilities. J Neurointerv Surg. 2021;13:865–868. doi: 10.1136/neurintsurg-2020-016783
49.
Salwi S, Cutting S, Salgado AD, Espaillat K, Fusco MR, Froehler MT, Chitale RV, Kirshner H, Schrag M, Jasne A, et al. Mechanical thrombectomy in ischemic stroke patients with severe pre-stroke disability. J Stroke Cerebrovasc Dis. 2020;29:104952. doi: 10.1016/j.jstrokecerebrovasdis.2020.104952
50.
Larsson A, Karlsson C, Rentzos A, Schumacher M, Abrahamson M, Allardt A, Brederlau A, Ceder E, Davidson M, Dunker D, et al. Do patients with large vessel occlusion ischemic stroke harboring prestroke disability benefit from thrombectomy? J Neurol. 2020;267:2667–2674. doi: 10.1007/s00415-020-09882-5
51.
Oesch L, Arnold M, Bernasconi C, Kaesmacher J, Fischer U, Mosimann PJ, Jung S, Meinel T, Goeldlin M, Heldner M, et al. Impact of pre-stroke dependency on outcome after endovascular therapy in acute ischemic stroke. J Neurol. 2021;268:541–548. doi: 10.1007/s00415-020-10172-3
52.
Leker RR, Cohen JE, Horev A, Tanne D, Orion D, Raphaeli G, Amsalem J, Streifler JY, Hallevi H, Bornstein NM, et al; NASIS-REVASC Study Group. Impact of previous stroke on outcome after thrombectomy in patients with large vessel occlusion. Int J Stroke. 2019;14:887–892. doi: 10.1177/1747493019841244
53.
Goldhoorn RB, Verhagen M, Dippel DWJ, van der Lugt A, Lingsma HF, Roos YBWEM, Majoie CBLM, Vos JA, Boiten J, van Zwam WH, et al; MR CLEAN Registry Investigators. Safety and outcome of endovascular treatment in prestroke-dependent patients. Stroke. 2018;49:2406–2414. doi: 10.1161/STROKEAHA.118.022352
54.
Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, et al; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20. doi: 10.1056/NEJMoa1411587
55.
Curtze S, Haapaniemi E, Melkas S, Mustanoja S, Putaala J, Sairanen T, Sibolt G, Tiainen M, Tatlisumak T, Strbian D. White matter lesions double the risk of post-thrombolytic intracerebral hemorrhage. Stroke. 2015;46:2149–2155. doi: 10.1161/STROKEAHA.115.009318
56.
Charidimou A, Turc G, Oppenheim C, Yan S, Scheitz JF, Erdur H, Klinger-Gratz PP, El-Koussy M, Takahashi W, Moriya Y, et al. Microbleeds, cerebral hemorrhage, and functional outcome after stroke thrombolysis. Stroke. 2017;48:2084–2090. doi: 10.1161/STROKEAHA.116.012992
57.
Ganesh A, Menon BK, Assis ZA, Demchuk AM, Al-Ajlan FS, Almekhlafi MA, Rempel JL, Shuaib A, Baxter BW, Devlin T, et al. Discrepancy between post-treatment infarct volume and 90-day outcome in the ESCAPE randomized controlled trial. Int J Stroke. 2021;16:593–601. doi: 10.1177/1747493020929943
58.
Ganesh A, King-Shier K, Manns BJ, Hill MD, Campbell DJ. Money is brain: financial barriers and consequences for Canadian stroke patients. Can J Neurol Sci. 2017;44:146–151. doi: 10.1017/cjn.2016.411
59.
Tedesco Triccas L, McLening B, Hendrie W, Peryer G. Is there a standard procedure for assessing and providing assistive devices for people with neuro-disabling conditions in United Kingdom? A nation-wide survey. Disabil Health J. 2019;12:93–97. doi: 10.1016/j.dhjo.2018.08.003
60.
Skolarus LE, Lin CC, Springer MV, Burke JF. Advance care planning among stroke survivors in the United States. Neurology. 2020;95:874–876. doi: 10.1212/WNL.0000000000010832
61.
Smith AK, Micco G. Serving the very sick, very frail, and very old: geriatrics, palliative care, and clinical ethics. Perspect Biol Med. 2017;60:503–518. doi: 10.1353/pbm.2017.0039
62.
Ganesh A, Luengo-Fernandez R, Wharton RM, Rothwell PM; Oxford Vascular Study. Ordinal vs dichotomous analyses of modified Rankin Scale, 5-year outcome, and cost of stroke. Neurology. 2018;91:e1951–e1960. doi: 10.1212/WNL.0000000000006554
63.
Quinn TJ, Dawson J, Lees JS, Chang TP, Walters MR, Lees KR; GAIN and VISTA Investigators. Time spent at home poststroke: “home-time” a meaningful and robust outcome measure for stroke trials. Stroke. 2008;39:231–233. doi: 10.1161/STROKEAHA.107.493320
64.
Shimmin C, Wittmeier KDM, Lavoie JG, Wicklund ED, Sibley KM. Moving towards a more inclusive patient and public involvement in health research paradigm: the incorporation of a trauma-informed intersectional analysis. BMC Health Serv Res. 2017;17:539. doi: 10.1186/s12913-017-2463-1
65.
Lo B. Behind closed doors: promises and pitfalls of ethics committees. N Engl J Med. 1987;317:46–50. doi: 10.1056/NEJM198707023170110
66.
Rahme R, Zuccarello M, Kleindorfer D, Adeoye OM, Ringer AJ. Decompressive hemicraniectomy for malignant middle cerebral artery territory infarction: is life worth living? J Neurosurg. 2012;117:749–754. doi: 10.3171/2012.6.JNS111140
67.
Goyal M, Ospel JM, Ganesh A, Marko M, Fisher M. Rethinking consent for stroke trials in time-sensitive situations: insights from the COVID-19 pandemic. Stroke. 2021;52:1527–1531. doi: 10.1161/STROKEAHA.120.031976
Information & Authors
Information
Published In
Copyright
© 2022 American Heart Association, Inc.
Versions
You are viewing the most recent version of this article.
History
Published online: 28 March 2022
Published in print: May 2022
Keywords
Subjects
Authors
Disclosures
| Writing group member | Employment | Research grant | Other research support | Speakers’ bureau/honoraria | Expert witness | Ownership interest | Consultant/advisory board | Other |
|---|---|---|---|---|---|---|---|---|
| Mayank Goyal | Foothills Medical Centre (Canada) | None | None | None | None | None | Microvention†; Medtronic†; Mentice† | None |
| Justin F. Fraser | University of Kentucky College of Medicine | University of Kentucky (departmental grants)*; American Heart Association (coinvestigator)* | None | None | None | Cerelux, LLC*; Fawkes Biotechnology* | Medtronic*; Penumbra*; Stream Biomedical* | None |
| Sepideh Amin-Hanjani | University of Illinois at Chicago | None | None | None | None | None | None | None |
| Negar Asdaghi | University of Miami Miller School of Medicine | None | None | None | None | None | None | None |
| Phillipe Couillard | University of Calgary (Canada) | None | None | None | None | None | None | None |
| Aravind Ganesh | University of Calgary Cumming School of Medicine (Canada) | None | None | None | None | None | None | None |
| Gillian L. Gordon Perue | University of Miami/Jackson Memorial Hospital | None | None | None | None | None | None | None |
| Steven M. Greenberg | Harvard University | None | None | None | None | None | None | None |
| Thabele M. Leslie-Mazwi | University of Washington | None | None | None | None | None | None | None |
This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
*
Modest.
†Significant.
| Reviewer | Employment | Research grant | Other research support | Speakers’ bureau/honoraria | Expert witness | Ownership interest | Consultant/advisory board | Other |
|---|---|---|---|---|---|---|---|---|
| Anne H. Aamodt | Oslo University Hospital (Norway) | None | None | None | None | None | None | None |
| Andrew P. Carlson | University of New Mexico | None | None | None | None | None | None | None |
| William Mack | Keck School of Medicine, University of Southern California | None | None | None | None | None | Penumbra Inc* | None |
| Aditya S. Pandey | University of Michigan | None | None | None | None | None | None | None |
This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
*
Modest.
Metrics & Citations
Metrics
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
- Endovascular thrombectomy for large vessel occlusion stroke in patients with pre-existing disability, Journal of NeuroInterventional Surgery, (jnis-2025-023208), (2025).https://doi.org/10.1136/jnis-2025-023208
- Heart failure, dementia is associated with increased stroke severity, in‐hospital mortality and complications, ESC Heart Failure, (2025).https://doi.org/10.1002/ehf2.15216
- Large Language Models–Supported Thrombectomy Decision-Making in Acute Ischemic Stroke Based on Radiology Reports: Feasibility Qualitative Study, Journal of Medical Internet Research, 27, (e48328), (2025).https://doi.org/10.2196/48328
- Current and Projected Burden of Ischemic Cerebrovascular Events: Nationwide Estimates From the Dijon Stroke Registry, France, Journal of the American Heart Association, 14, 2, (2025)./doi/10.1161/JAHA.124.037925
- Utilization, Workflow, and Outcomes of Endovascular Thrombectomy in Patients With vs Without Premorbid Disability in a National Registry, Neurology Clinical Practice, 14, 6, (2024).https://doi.org/10.1212/CPJ.0000000000200341
- Understanding physician preferences about combined thrombolysis and thrombectomy in patients with large vessel occlusion: An international cross-sectional survey, Journal of Stroke and Cerebrovascular Diseases, 33, 12, (108022), (2024).https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.108022
- Care Quality and Outcomes of Ischemic Stroke in Patients With Premorbid Dementia: Get With The Guidelines-Stroke Registry, Stroke, 55, 12, (2901-2905), (2024)./doi/10.1161/STROKEAHA.124.049027
- Ten-year trends, disparities, and clinical impact of stroke thrombectomy and thrombolysis: A single center experience 2012-2021, Journal of Stroke and Cerebrovascular Diseases, 33, 10, (107914), (2024).https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.107914
- Reperfusion therapy and risk of post-stroke delirium, Neurological Research, 47, 1, (1-6), (2024).https://doi.org/10.1080/01616412.2024.2403484
- Fluid excess on intensive care unit after mechanical thrombectomy after acute ischemic stroke is associated with unfavorable neurological and functional outcomes: An observational cohort study, European Stroke Journal, 10, 1, (74-83), (2024).https://doi.org/10.1177/23969873241271642
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
Purchase this article to access the full text.
eLetters(0)
eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.
Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.