Edited by: Bruce Campbell, University of Melbourne, Australia
Reviewed by: Christian H. Nolte, Charité – Universitätsmedizin Berlin, Germany; Benjamin B. Clissold, Monash University, Australia
Specialty section: This article was submitted to Stroke, a section of the journal Frontiers in Neurology
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Endovascular treatment of anterior circulation large vessel occlusion in the elderly population presents special challenges and opportunities. In this review, we discuss the published literature regarding thrombectomy in elderly patients and also discuss specific issues related to treatment in this patient population. In summary, while the overall outcomes following thrombectomy in elderly patients are worse than following thrombectomy in younger patients, there appears to be a similar benefit as in young patients. While there are challenges with successfully delivering thrombectomy in older patients, age alone should not be an independent exclusion from thrombectomy.
Acute ischemic stroke caused by large vessel occlusion (LVO) in the anterior circulation is the leading cause of adult disability in the developed world. Until recently, the only therapy proven to improve outcomes for all ischemic stroke patients was the intravenous (IV) administration of tissue plasminogen activator (tPA), which can be administered up to 4.5 h from the onset of symptoms or when the patient was last known normal. Unfortunately, those strokes caused by occlusion of the large intracranial vessels, such as the internal carotid artery (ICA) and proximal middle cerebral artery (MCA), had low rates of response to IV tPA, and subsequently, poor outcomes (
The next revolution in stroke began in 2015, when five randomized trials all showed that rapid mechanical thrombectomy, primarily using stent-retriever devices, significantly improves outcomes in anterior circulation (ICA and MCA) LVO stroke patients (
The application of this highly effective therapy to the older population presents unique challenges, however. The incidence of stroke is higher in the older population (
Several single and multicenter case series have been published examining the question of whether there is a benefit of treatment in the elderly (
Singer evaluated 362 patients in the multicenter ENDOSTROKE registry and showed a significant dependence of age on outcomes. Only 17% of patients in the oldest quartile (77–94 years old) achieved independence at 90 days, compared with 37% in those 69–67 years old, 47% in the 57- to 68-year-old group, and 60% in those younger than 57. In addition, there was an increasing rate of poor outcome despite recanalization with age, reaching 53% in the oldest age group. They suggested that medical comorbidities, procedural issues such as tortuous anatomy, the use of general anesthesia, and impaired collaterals all played a role in these observed poor outcomes (
Khan and colleagues examined the impact of treatment on nonagenarians, compared with the younger cohort (
A meta-analysis by Duffis examined this specific issue and found higher rates of symptomatic intracranial hemorrhage and lower rates of good functional outcome in patients older than 80 (
In summary, most single armed trials of thrombectomy in anterior circulation stroke show worse outcomes with older age as compared with younger cohorts.
However, all of the aforementioned series were reporting outcomes of patients treated with thrombectomy. What about randomization compared with medical therapy alone? Among the current generation of randomized thrombectomy trials, prespecified analysis based on an age threshold shows significant benefit in older subgroups in the ESCAPE and MR CLEAN trials (divided as 80 years or older vs. younger) and in the SWIFT-PRIME (divided as 70 years or older vs. younger) trial, with no heterogeneity of benefit. In the REVASCAT trial, there was not a difference between medical and endovascular therapy in the older subgroup, but this difference was not statistically significant. These results are summarized in Table
Summary of outcomes in older patients in seven randomized trials of modern endovascular stroke thrombectomy (primarily using stent-retriever devices).
Trial | Patients | Odds ratio for favorable outcomes with thrombectomy | Independence at 90 days (mRs 0–2) in older and younger groups; endovascular vs. control |
---|---|---|---|
MR CLEAN ( |
500 | Age <80 years: 1.6 |
Not reported |
ESCAPE ( |
316 | Age ≤80 years: 3.0 |
Age ≤80 years: 59.3 vs. 33.4% |
REVASCAT ( |
206 | Age ≤70 years: 2.5 |
Age ≤70 years: 52.5 vs. 23.3% |
SWIFT-PRIME ( |
191 | Age <70 years: 1.67 |
Age <70 years: 65 vs. 40% |
THRACE ( |
402 | Age <70 years: 1.6 |
Not reported |
DAWN ( |
206 | Age <80 years: 1.9 |
Age <80 years: 54 vs. 17% |
In summary, while older patients may have worse outcomes overall, there is no heterogeneity of treatment effect seen by age. Thrombectomy is just as effective in elderly patients as it is in younger ones. In addition, the outcomes with medical therapy alone are dismal in older patients, and rapid, successful thrombectomy may by the best chance the older patients have at a favorable outcome.
Ultimately, deciding to take the patient to the angiography suite for thrombectomy means that the treating team feels the procedure is likely to improve the patient’s chance of meaningful neurologic recovery. In the preprocedure time period, this is dependent on the patient’s baseline functional status, as well as the status of the brain tissue, as assessed by brain imaging.
Almost all the patients in the recent randomized trials of thrombectomy were required to be functionally independent for enrollment, typically defined as modified Rankin scale score of 0 or 1. As such, in patients with preexisting disability, randomized data comparing the outcomes with thrombectomy vs. best medical therapy is lacking. Elderly patients may have a higher rate of preexisting disability, which can make the treatment decision more difficult. Pohjasvaara examined the level of pre- and poststroke disability in a cohort of 486 patients in Helsinki. They found higher levels of prestroke disability in the group aged 71–85 as compared with those aged 55–70 (
There can be additional difficulties in establishing a functional baseline in patients who come from a non-home living situation. Patients may be in assisted living facilities requiring varying amounts of assistance with activities of daily living. However, in the time critical period between hospital arrival and treatment decision, it may be difficult to elucidate how functional the patient was prestroke, especially when family is not available to provide additional history. These additional items should not delay thrombectomy, but may be difficult to obtain in a timely fashion. It is also possible that patient age may play a role in determining if a patient should be transferred from a non-thrombectomy capable center to one where they can be treated, although data are lacking in this regard.
In summary, preexisting disability is more common in elderly patients and would have excluded them from most randomized trials of thrombectomy. While preexisting disability is not an absolute contraindication to treatment, the team evaluating the patient should do their best to assess prestroke functional status and make an individualized decision in elderly patients with preexisting disability.
Baseline brain parenchymal imaging (with non-contrast CT) and vessel imaging [with CT angiography (CTA)] should be the minimum standard on all stroke patients, regardless of severity (
Preexisting leukoaraiosis, typically more prevalent in an older patient, has been associated with worse outcomes after thrombectomy as well (
Some series have suggested an age-dependent threshold may be accurate for the degree of baseline infarct beyond which endovascular thrombectomy is unlikely to help the patient (
In summary, when evaluating pretreatment imaging one may need to take patient age into account, especially as it pertains to the evaluation of core infarct volume, regardless of modality.
In the HERMES dataset, it was beneficial to use conscious sedation or local anesthesia as opposed to general anesthesia. This effect may be more so in the elderly population, as there are additional risks from anesthesia. Some recent studies, however, have suggested no difference in outcomes between sedation and general anesthesia (
When using propofol for procedural sedation during endoscopy, Heuss showed that while elderly patients (age >70 years) had slightly higher rates of short periods of oxygen desaturation below 90%, and an overall decrease in oxygen saturation below 5%, especially in those above the age of 85, but they felt that overall, propofol is safe for sedation in the elderly (
To summarize, while no study has demonstrated a benefit to using general anesthesia over conscious sedation, nor are there substantial data evaluating the relationship of mode of anesthesia with outcomes in older patients undergoing endovascular stroke thrombectomy, it may be preferable in patients of all ages to use conscious sedation whenever possible.
Intraprocedurally, elderly patients pose anatomic challenges, primarily due to greater tortuosity of their vasculature. Placement of the large bore guiding catheters, including balloon guide catheters, can be more difficult in the elderly population. In extreme cases, direct carotid puncture can be performed, but also likely introduces additional risk. In the NASA registry, procedure times were slightly longer in the elderly cohort, which may be on the basis of the arterial anatomy (
Post revascularization, critical issues include the need to closely follow the patient’s neurologic exam as well as hemodynamic parameters to potentially minimize the likelihood of intracranial hemorrhage. In elderly patients treated under general anesthesia, postoperative delirium may be common and can cloud the neurologic examination (
Patients with higher baseline systolic blood pressure have higher rates of symptomatic intracranial hemorrhage after systemic thrombolysis. As such, current recommendations are to maintain blood pressure below 185 systolic and 110 diastolic following systemic thrombolysis (
Among the main unanswered questions, regarding thrombectomy is whether our systems of care are sufficiently well enough organized to provide access to this therapy. Should patients be routed in the field to endovascular capable centers, bypassing closer, non-endovascular capable centers? (
In summary, while the overall benefit of thrombectomy is similar in older and younger patients, elderly patients are less likely to achieve functional independence. This may be on the basis of slightly higher levels of prestroke disability, decreased functional reserve, and diminished tolerance to larger core infarcts before recanalization. Age alone should not exclude patients from thrombectomy, but the treating team should be aware of and prepared for factors, which make treatment in this group potentially more challenging.
Both authors contributed to literature review, manuscript revision, and final review.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.