Stroke in the Elderly ppt

Impact, burden and risk factors ▪ The number of centenarians ≥100 years is projected to increase 15-fold 6 ▪ The management of stroke in the elderly is becoming an important considerat

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Stroke in the Elderly

Stephen Davis, Kennedy Lees, Richard Lindley

Stroke in the Elderly

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Table of contents

1 Impact, burden and risk factors 3

2.3 Outcomes of thrombolytic therapy in the elderly 20

2.5 Current recommendations for the elderly 25

3.1 Fundamentals of long-term post-stroke care 31

3.3 Challenges of rehabilitation and the elderly 41

Stroke in the Elderly

Stroke in the Elderly

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1 Impact, burden and risk factors

1 Impact, burden and risk factors

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1 Impact, burden and risk factors

1.1 Prevalence and incidence

▪ According to the World Health Organisation (WHO), approx- imately 15 million people suffer from stroke each year (1)

▪ Of these, 5 million die and another 5 million are permanently disabled (Figure 1)

1 Impact, burden and risk factors

Learning objectives

impact of stroke in the elderly.

what challenges are involved in this process.

15 million people

suffer from stroke

each year

▪ Mortality rates for coronary heart disease and acute myocardial infarction continue to decrease, but mortality rates for stroke have not changed significantly during the past 10 years

▪ Around the world, the majority of strokes (75% to 89%) occur in those over 65 years of age (Figure 2) (2, 3)

▪ For each decade of life after age 55, the stroke rate doubles in both men and women (4)

1 Impact, burden and risk factors

The majority of

strokes occur in

the over 65s

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1 Impact, burden and risk factors

1.2 Role of age in outcomes and burden

▪ Stroke is the 6th leading cause of disability or burden worldwide

in terms of DALYS (disability-adjusted life years) (1)

▪ This represents a loss of 46.6 million years of healthy life (1)

▪ Stroke also ranks as the third most common cause of burden in middle- and high-income countries, following depressive disorders and ischaemic heart disease (1)

▪ These 3 diseases are predicted to move up the rankings to become 3 of the 4 leading causes of disease and injury burden

by 2030 (1)

▪ In a study of individuals aged 65 and older in 7 low- and middle- income countries (including China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru), stroke was found to be the second-largest contributor to disability, following dementia (5)

Figure 3: Contribution of stroke to disability

Stroke is the 6th

leading cause

of disability or

burden worldwide

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1 Impact, burden and risk factors

▪ Paralysis or weakness of the limbs was also found to be a large contributor to disability, although many of these cases were thought to be related to stroke (5)

▪ Furthermore, it was found that in these 7 countries, stroke was the 4th most common diagnosis, following hypertension, diabetes and dementia (5)

▪ An ageing population will increase the prevalence of stroke and its associated burden

▪ By 2050, the global population over 60 years of age is projected

to approach 2 billion, compared with 629 million in 2002 (Figure 4) (6)

▪ 54% of those aged >60 years reside in Asia; 24% in Europe

▪ The fastest growing segment of the older population is people aged ≥80 years, which comprised 12% of the world population

in 2002 and is projected to reach 19% in 2050 (6)

With the aging

population,

the prevalence

of stroke will

increase

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1 Impact, burden and risk factors

▪ The number of centenarians (≥100 years) is projected to increase 15-fold (6)

▪ The management of stroke in the elderly is becoming an important consideration for healthcare professionals and providers, not only because of increasing incidence and prevalence, but also due to poorer outcomes in this age group

– Medical outcomes following stroke, such as disability and mortality, have been noted to worsen with age

– Those over 80 years of age, who have a stroke, are more likely to die in hospital and less likely to have favourable long-term recovery compared to younger survivors

– A study by Olindo and colleagues, of all patients with first-ever stroke, observed that those ≥85 years of age had significantly greater disability approximately 1 week after stroke and significantly higher mortality during the first 2 months after stroke compared with those <85 years (Figure 5) (7)

– Among those who survived the first 2 months, older survivors were more likely to have moderate to severe disability than younger survivors (7)

– Poor health and pre-stroke disability in the elderly may contribute to the poorer outcome in this age group (7)

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1 Impact, burden and risk factors

▪ Post-stroke differences between elderly and younger survivors persist following stroke

▪ Results from the Copenhagen Stroke Study showed that survival

is significantly lower among those ≥85 years of age compared with younger survivors through more than 5 years after stroke (Figure 5) (8)

Figure 5: Differences in survival persist for years following stroke

▪ Elderly survivors are more likely to experience certain post- stroke disabilities compared with younger survivors, including (9):

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1 Impact, burden and risk factors

1.3 Ageing-related risk factors

▪ There are significant ageing-related risk factors for stroke, and risk factor profiles and mechanisms of ischaemic injury differ between younger and elderly patients (Figure 6) (10)

▪ The incidence of ischaemic stroke is higher in men <80 years compared with women, whereas after 80 years of age, women have a higher incidence (4,8)

▪ Risk factors for ischaemic stroke, such as atrial fibrillation, congestive heart disease, and carotid artery stenosis, increase sharply with age (10)

▪ In addition, age-related changes within the central nervous system may render the elderly more sensitive to ischaemic damage (10)

▪ Axonal pathways are injured in most strokes and contribute importantly to clinical deficits (10)

▪ Central nervous system atrophy that begins in midlife may reduce cerebrovascular reserves, leaving the brain more susceptible to vascular insufficiency and ischaemic injury to these pathways (11)

Risk factor profiles

for stroke differ

between elderly

and younger

patients

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1 Impact, burden and risk factors

1.4 Defining the elderly population

▪ Studies vary widely in the age ranges used to designate older

or elderly patients; from 60 to 65 years of age, to 75, 80, or 85 years of age

▪ Even within these ranges of older patients, the incidence, prevalence, risk factors, and prognosis for stroke can differ

▪ A study of cardiovascular risk profiles in patients older and younger than 85 years found that congestive heart failure, chronic renal disease, previous cerebrovascular disease and atrial fibrillation were significantly associated with stroke in the very old, whereas risk factors such as diabetes, hypertension, hyperlipidaemia and heavy smoking were less relevant to older patients (Figure 7) (12)

▪ Similar results were found in a study, which looked at patients younger and older than 80 years

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1 Impact, burden and risk factors

▪ It is worrying to find that elderly stroke survivors may not receive the same level of care as younger survivors

▪ Results from a European Union Concerted Action study in 7 countries involving 4,499 patients who were hospitalised for

a first stroke found that the use of investigations during inpatient care was significantly lower among older survivors (9)

▪ Significantly fewer survivors 85 years of age or older received brain imaging, Doppler examination, echocardiogram, and angiography (Figure 8) (9)

▪ Surgical interventions, such as carotid surgery, were also less frequently performed in the elderly (9)

▪ Beyond these initial assessments, evidence suggests that elderly survivors have less access to other key elements of post-stroke care

Figure 8: Older patients may receive less care

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1 Impact, burden and risk factors

▪ An evaluation of stroke services in the United Kingdom showed that those 85 years of age or older were less likely to be treated

in a stroke unit or to receive secondary prevention, and also less likely to receive some aspects of rehabilitation

▪ Each of these elements of post-stroke care has shown benefits regardless of age

1.5 Summary

▪ Stroke has high global prevalence that is increasing with the ageing of worldwide populations, and which is associated with

a high economic burden

▪ With increased age, the incidence of stroke increases while outcomes worsen

▪ This may be related to the fact that certain risk factors for ischaemic stroke, as well as age-related changes within the central nervous system, are increased with age

▪ The elderly and the oldest old are subject to different conditions and risks, and should be examined separately for unique risk factors and patterns so that acute and long-term post stroke care can be optimised for this growing population

Mortality rates for stroke continue to decreaseAround the world, the majority of strokes (75% to 89%) occur

in those over 65 years of age For each decade of life after age 55, the stroke rate doubles in both men and women

Surgical interventions, such as carotid surgery, are more frequently performed in the elderly

Elderly survivors have less access to other key elements of post-stroke care

Patients 85 years of age or older were less likely to be treated

in a stroke unit or to receive secondary prevention, and also less likely to receive some aspects of rehabilitation

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1.6 References

1 World Health Organization The Global Burden of Disease 2004 Update Geneva,

Switzerland: WHI Press; 2008.

2 Feigin VL, Lawes CM, Bennett DA, Anderson CS Stroke epidemiology: a review

of population-based studies of incidence, prevalence, and case-fatality in the late

20 th century Lancet Neurol 2003;2(1):43-53.

3 Rosamond W, Flegal K, Furie K, et al Heart disease and stroke statistics 2008 update: a report from the American Heart Association Statistics Committee and

Stroke Statistics Subcommittee Circulation 2008;117(4):e25-146.

4 Rojas JI, Zurru MC, Romano M, et al Acute ischemic stroke and transient ischemic attack in the very old risk factor profile and stroke subtype between patients older

than 80 years and patients aged less than 80 years Eur J Neurol 2007;14(8):

895-899.

5 Sousa RM, Ferri CP, Acosta D, et al Contribution of chronic diseases to disability

in elderly people in countries with low and middle incomes: a 10/66 Dementia

Research Group population-based survey Lancet 2009;374(9704):1821-1830.

6 United Nations, Population Division, Department of Economic and Social Affairs POPULATION AGEING-2002 Presented at: the Second World Assembly on Ageing; 2007; Madrid, Spain.

7 Olindo S, Cabre P, Deschamps R, et al Acute stroke in the very elderly Stroke

2003;34:1593-1597.

8 Kammersgaard LP, Jorgensen HS, Reith J, et al Short- and long-term prognosis

for very old stroke patients The Copenhagen Stroke Study Age Ageing 2004;

33(2):149-154.

9 DiCarlo A, Lamassa M, Pracucci, et al Stroke in the very old: clinical presentation and determinants of 3-month functional outcome: A European perspective

European BIOMED Study of Stroke Care Group Stroke 1999;30(11):2313-2319.

10 Chen RL, Balami JS, Esiri MM, et al Ischemic stroke in the elderly: an overview of

evidence Nat Rev Neurol 2010;6(5):256-265.

11 Baltan S, Besancon EF, Mbow B, et al White matter vulnerability to ischemic injury

increases with age because of enhanced excitotoxicity J Neurosci 2008;28(6):

1479-1489.

12 Arboix A, Miguel M, Ciscar E, et al Cardiovascular risk factors in patients aged 85

or older with ischemic stroke Clin Neurol Neurosurg 2006;108(7):638-643.

1 Impact, burden and risk factors

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2 Acute stroke care

2 Acute stroke care

▪ Intravenous treatment with alteplase, started soon after stroke onset, has been shown to be safe and effective in randomised controlled trials (2,3)

▪ An analysis of pooled data from all trials including the recent ECASS 3 study confirmed that alteplase has a favourable risk-benefit ratio up to 4.5 hours from stroke onset (Figure 1) (4)

2 Acute stroke care

Alteplase is the

only approved clot

lysis therapy for

acute ischaemic

stroke

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▪ There is a positive association between mortality and time

to start of treatment but no significant increase in deaths unless treatment is commenced beyond 4.5 hours (4)

▪ The risk of large intracranial haemorrhage does not appear to

be significantly associated with time to initiation of treatment (4)

2 Acute stroke care

2.2 Very elderly in clinical trials

▪ Inevitably, compared to the young, older people suffer more from any health challenge and have poorer outcomes This also applies to patients who receive thrombolysis

▪ A prospective study of stroke patients treated with intravenous alteplase showed that those aged 80 and older had more than twice the mortality rate compared with patients younger than

80 years, and were only half as likely to achieve a favourable outcome (5)

▪ However, this age difference likely reflects confounding factors such as case mix and comorbidity as we will see later

▪ Unfortunately, the elderly, who represent a significant and increasing proportion of patients who might be eligible for and benefit from thrombolytic treatment, have been under- represented in the large, randomised, controlled trials of alteplase (6)

▪ Only 137 patients aged 80 years or older were available for pooled analysis

▪ With only small numbers of very elderly patients in the NINDS and other trials, analysis of the randomised controlled trial data in this sub-population is equivocal

▪ It reveals comparable benefits from treatment in the young and elderly cohorts after adjusting for differences in prognostic

The elderly are

under-represented

in clinical trials

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2 Acute stroke care

▪ The unadjusted numbers for the modified Rankin scores are slightly lower in the elderly cohort; however, more of the elderly patients with severe stroke were allocated to alteplase inter- vention rather than placebo (7)

Figure 2: Outcomes for alteplase versus placebo in randomised controlled trials

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2 Acute stroke care

2.3 Outcomes of thrombolytic therapy in the elderly

▪ An analysis of patients in the large Virtual International Stroke Trials Archive, VISTA reveals that the benefit of alteplase therapy is comparable in elderly and young patients and extends across the range of possible outcomes (Figure 3) (7)

▪ This analysis not only showed the influence of age alone on outcome - the elderly have much higher short-term mortality than younger patients and less chance of good outcome - but also that the effect of treatment with alteplase is just as great in older patients as in patients aged under 80 years (Figure 3) (7)

▪ While randomised controlled trial data of thrombolysis efficacy have limited numbers of older adults, more comprehensive outcome data from this cohort come from published but uncontrolled cohort studies and analyses of stroke registries

Figure 3: Outcomes in thrombolysed patients versus controls: VISTA

VISTA reveals that

alteplase benefits

are comparable

in young and old

patients

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2 Acute stroke care

▪ Although the European Safe Implementation of Thrombolysis

in Stroke Monitoring Study, known as SITS-MOST, excluded patients 80 years and older due to age restrictions of the European marketing licence for alteplase (8), thrombolysis outcomes for older patients have been included in the SITS International Stroke Thrombolysis Register (SITS-ISTR) (9)

▪ A comparison of alteplase-treated patients in the SITS registry versus control patients from VISTA reported comparable benefit of thrombolysis in elderly and younger patients after adjustment for baseline prognostic factors (10)

Figure 4: Thrombolysis efficacy similar across age groups in VISTA and SITS-ISTR

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2 Acute stroke care

▪ An analysis of safety of intravenous alteplase use in the elderly by the SITS group confirms that although bleeding after thrombolysis may be less common in younger patients, the very elderly – those aged over 80 – are not at higher risk than 60 to 80 year olds (11)

▪ In fact, serious bleeds may become less common in very elderly patients, perhaps because clinicians are more cautious

in offering treatment or because intracerebral pressure effects are less serious in older patients with some brain atrophy

SITS shows that

patients >80 years

are not at higher

risk with alteplase

therapy than those

<80 years

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2 Acute stroke care

2.4 Newer treatments for stroke

▪ Newer stroke treatments have limited safety and efficacy data

Intra-arterial finbrinolysis

▪ The second Prolyse in Acute Cerebral Thromboembolism study (PROACT-II), which looked at inter-arterial fibrinolysis in stroke victims, excluded patients aged 85 years and older (12)

Endovascular treatments

▪ Endovascular treatments, such as intravenous and intra- arterial thrombolysis, mechanical thrombectomy with the Penumbra or MERCI retriever devices, and angioplasty with expandable stents are considered by some to be promising alternative treatments for patients ineligible for standard intravenous thrombolytic therapy However, just as there are

no randomised studies in the young, there are virtually no efficacy and safety data available for these therapies in patients over 80 years old (6)

▪ This age group was even excluded from the uncontrolled Interventional Management of Stroke study (IMS II) (13)

Hemicraniectomy

▪ Studies of hemicraniectomy, a technique used to relieve swelling secondary to cerebral artery infarction, also lack data

There is currently

very little efficacy

and safety data

on endovascular

treatments in the

elderly

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2 Acute stroke care

▪ After the observed success of hemicraniectomy in young patients (17), a second Destiny (decompressive surgery for the treatment of malignant infarction of the middle cerebral artery) trial, DESTINY-II, is being conducted solely in patients older than 60 years to remedy this gap (18)

▪ The primary endpoint of this prospective, randomised study

is the effect of decompressive hemicraniectomy versus more conservative intensive care treatment on disability at 6 months, based on the modified Rankin Scale, with secondary out comes at 1 year in disability, functional neurological deficit, and quality of life (18)

Neuroprotective approaches

▪ Various proposed neuroprotective approaches to protect the ischaemic penumbra have shown promise in animals but have

so far been unsuccessful in humans

▪ The selection of agents for clinical testing may have been

Figure 5: Age limits of hemicraniectomy trials