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Why too much medicine is a problem for
many older people
SYDNEY MEDICAL SCHOOL
A/Prof Sarah Hilmer, BScMed(Hons) MBBS(Hons) FRACP PhD
Departments of Aged Care and Clinical Pharmacology, RNSH
Northern Clinical School, Sydney Medical School
Kolling Institute of Medical Research
Why too much medicine is a problem for many
older people
› Too much for what?
- To achieve therapeutic aims
› According to who?
- Patients/caregivers
- Clinicians
› What is the problem?
- Medicines not helping achieve aims?
- Researchers
- Policy makers
- Medicines causing harm?
- Cost of medicines?
› How assessed?
- Subjectively
- Objectively
Why too much medicine is a problem in some
older people
› Who are we treating?
› What are the aims of treatment?
› What is the evidence that medicines can help?
› What is the evidence that medicines can harm?
› What happens if we stop treatment?
Who are we treating?
- Characteristics of our ageing population
- Multi-morbidity
- Geriatric syndromes
4
Ageing Population
Growing and highly variable
Australians aged >65 years:
› 36% born overseas
› 81% identified with a religion
› 2.4% had no schooling; 61%
completed at least Year 10; 28%
Year 12
› 19% have profound or severe
disability
Australian Bureau of Statistics 2071.0 - Reflecting a Nation: Stories from the 2011 Census, 2012–2013
High Prevalence of Multi-morbidity
High prevalence of geriatric syndromes
Non-specific, multi-factorial, common risk factors, frequently co-exist, poor outcomes
Falls
Iatrogenesis
Confusion
Incontinence
Functional
decline
Frailty
7
What are the aims of treatment?
According to consumers, health care workers and policy makers
8
What do consumers want?
What patients want varies between individuals and over time
9
What do clinicians want?
› Evidence-based practice
› Ethical practice
- Beneficence
- Non-maleficence
- Autonomy
www.zazzle.com
healthwise-everythinghealth.blogspot.com
10
What do policy makers want?
National Medicines Policy
http://www.health.gov.au/internet/main/publishing.nsf/Content/National+Medicines+Policy-1
11
Generalisations
12
‘Successful Ageing’
› Absence or avoidance of disease and risk factors for disease,
› Maintenance of physical and cognitive functioning, and
› Active engagement with life (including maintenance of autonomy and
social support)
13
Therapeutic aims often vary with development of
multi-morbidity, disability and geriatric syndromes
Increasing co-morbidities
Increasing disability
Disease
Geriatric syndromes
Prevention
Disease
Last year of life
Management Maintain
Function
Palliation
14
Evidence that medicines help older people
15
Medicines help people get old
Medicines can help prevent and treat disease in
older people
PRINCIPLES
› Multiple risk factors for disease
› Risk factors may change as get older
› Pathophysiology of disease may change as get older
› Prevalence of disease increases in old age so smaller changes in relative
risk can have a bigger impact on absolute risk of disease
› Generally better evidence in secondary prevention than in primary
prevention in older people
› Limited high quality evidence from older patients, especially from older
people with multi-morbidity and geriatric syndromes
17
Medicines for treatment of older people with
multi-morbidity
› Clinical practice guidelines do not address multi-morbidity
- Evidence based and RCTs generally exclude people with multi-morbidity
› Following single disease guidelines results in
- Drug-drug and drug-disease interactions
- Significant time and cost of care
› Patients have multiple causes of morbidity and mortality
› Therapeutic competition
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Treatment of older people with geriatric syndromes
› Geriatric syndromes may be outcomes of medicines use:
- Medications may increase or decrease the risk of geriatric syndromes
› Geriatric syndromes may modify the use and effects of medicines:
- Poorly understood
- What is their impact on:
- Therapeutic aims/indications?
- Pharmacokinetics?
- Pharmacodynamics?
- Efficacy?
- Safety?
Geriatric syndromes and treatment may influence
clinical outcomes independently
Beta blocker
Cardiac
failure
Age
Comorbidity
Geriatric
syndrome,
eg frailty
Death
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Geriatric syndromes may confound the association
between treatment and clinical outcomes
Beta blocker
Cardiac
failure
Age
Comorbidity
Geriatric
syndrome,
eg frailty
Death
21
Geriatric syndromes and may modify the effects of
drug treatment on outcomes
Beta blocker
Cardiac
failure, nonfrail
Age
Comorbidity
Cardiac
failure, frail
Death
22
What is the impact of frailty on medicines use,
pharmacokinetics, pharmacodynamics,
safety and efficacy?
What is the impact of frailty on medicines use,
pharmacokinetics, pharmacodynamics,
safety and efficacy?
Definitions of Frailty:
- Frailty Phenotype: ≥3 of unintentional weight
loss, self-reported exhaustion, weakness, slow
walking speed, low physical activity
- Frailty Index: deficit accumulation
- Many others
Frailty Impacts on Drug Use:
Older Patients with Atrial Fibrillation
220 patients aged ≥70 years admitted to a Sydney teaching hospital
Frailty defined using Reported Edmonton Frail Scale (deficit accumulation)
Percentage within group
100%
90%
80%
70%
None
Aspirin/Other
Warfarin
60%
50%
40%
30%
20%
10%
0%
Frail
Frail
Admission Discharge
Frail (n = 140)
Not Frail
Not Frail
Admission Discharge
Not Frail (n = 80)
Frail participants were prescribed
warfarin less than non-frail on
admission (p=0.002) and discharge
(p<0.001)
Perera et al., Age and Ageing, 2009
Problems with medicines associated with dosing:
Pharmacokinetics in old age and frailty
Pharmacokinetic
Parameter
Ageing
Frailty
Absorption
↔
?
Distribution
↓water ↑fat
↓albumin
↓↓water ↑↑fat
↓↓ albumin
Metabolism
↓ phase 1
? phase 2
?↓ phase 1
↓ phase 2
Excretion
↓
↓↓
Ieet.org
Blog.ecaring.com
Hilmer et al., FCP, 2007
Changes in drug response:
Pharmacodynamics in old age and frailty
 Different sensitivity to different drug classes
 Less physiologic reserve
Example: Response to metaclopramide in old age and frailty
Frail elderly intravenous
Frail elderly intravenous
Wynne et al., Age and Ageing, 1999
Statins and clinical outcomes in robust and frail older men:
Concord Health and Ageing in Men Project
Kaplan-Meier survival curves for the time until institutionalisation and death
by reported statin exposure and frailty
Gnjidic D et al. BMJ Open 2013;3:e002333
What is the evidence that medicines can harm
older people?
29
Harm from medicines in older people
BETTER UNDERSTOOD THAN BENEFITS
› Treatment burden: time, cost
› Adverse drug reactions
› Impaired physical and cognitive
function
› Geriatric syndromes
› Hospital admissions
› Death
Debra-international.org
Growing consumer awareness of harms
Medication may cause elderly to become frail
Date May 4, 2013
Amy Corderoy, Health Editor, Sydney Morning Herald
The cocktail of drugs commonly prescribed to older people could be hastening their ageing, according to
experts who say despite the risks of over-medication the problem is getting worse.
‘There is [also] the potential for battery or medical negligence cases to be brought.’
A case for elderly to ditch long-term use of medication
Julie Robotham Medical Editor, Sydney Morning Herald
January 5, 2009
ELDERLY people receive no benefit from long-term use of many common medicines, and their health may
even improve if they stop taking them, a University of Sydney study has found.
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Polypharmacy
› Polypharmacy is associated with every other geriatric
syndrome
› Consumers, clinicians and policy makers need more
specific risk assessment tools to guide prescribing
Chrisjohnsonpt.com
Dangersofpolypharmacy.worldpress.com
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Beyond Polypharmacy:
Measuring the risk associated with medicines in older people
Pharmacological measures of exposure to investigate associations of
medicines with adverse clinical outcomes
› Study medicines that are likely to impact on specific outcomes based on:
- their pharmacology
- the population studied
› Quantify exposure in terms of:
- Number of drugs of interest
- Strength of their effects
- Dose of drugs of interest
- Impact of any pharmacokinetic or pharmacodynamic changes in population
studied
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Interactive Concentric Model of Geriatric Syndromes:
Example of falls
Risk Factor
Synergism
Anti-hypertensives
Autonomic
Degeneration
Postural Hypotension
Visual Impairment
Sedatives
Proximal myopathy
Falls
Combinations of Medications Associated with
Geriatric Syndromes
Geriatric Syndrome
Measure of Cumulative
Medication Exposure
Falls
Impaired
Physical
Function
Falls Risk Increasing Drugs
x
x
CNS Medicines
x
x
Impaired
Cognitive
Function
x
Sedative Load
x
Anticholinergic Burden
x
x
x
x
Drug Burden Index
x
Adapted and updated from Hilmer and Gnjidic, CPT 2009
In older people, higher Drug Burden Index is
associated with:
Drug Burden Index measures total exposure (including dose) to medicines with
sedative and anticholinergic effects
Outcome
Older populations studied
Impaired physical function
Community dwelling, USA,
Community dwelling men, Australia
Community dwelling, Finland
Inpatients, UK
Falls
Residential aged care, Australia
Hospitalisation
Inpatients, UK
Community dwelling, Finland
Mortality
War Veterans, Australia
Community dwelling, Finland
Frailty
Community dwelling men, Australia
Hilmer et al Am J Med, 2009, Gnjidic et al., BJCP 2009, Wilson et al., JAGS 2011, Lowry et al., J Clin Pharmacol, 2011,
Loonnroos et al., Drugs and Aging, 2012; Gnjidic et al., CPT 2012 ; Gnjidic et al., Annals of Internal Medicine, 2012.
Deprescribing: stopping treatment
37
Deprescribing:
When too much treatment is a problem
CONSIDER AT EVERY REVIEW
› Triggers to deprescribe:
- Drug triggers: polypharmacy, Drug Burden Index and others
- Patient triggers: multi-morbidity, geriatric syndromes, terminal illness
- For each individual: drug not helping achieve aims or causing harm
› How to deprescribe:
- Collaborative, active process involving consumers and clinicians
› Outcomes of deprescribing:
- No immediate change in condition
- Resolution of adverse drug reactions, improved function/quality of life
- Withdrawal and discontinuation syndromes
Le Couteur et al., Aust Prescriber, 2012; Hilmer et al., Aust Fam Physician 2012
Why is too much medicine a problem in some
older people?
› Emerging evidence on how to treat older people with multi-morbidity and
geriatric syndromes to optimise clinical outcomes
› Two travelling shoe salesmen went to Africa in the 1900s
- Sent home telegrams,
- “Situation hopeless – they don’t wear shoes”
- “Glorious opportunity – they don’t have any shoes”
› The complexity of treatment of older adults provides consumers, clinicians,
students, researchers and policy makers with the opportunity to apply the
art of medicine and to develop the science required to improve treatment
outcomes for older people.
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› Collaborators
- Dr Danijela Gnjidic
- Prof David Le Couteur
- Prof Andrew McLachlan
- Dr Darrell Abernethy
- Prof Sirpa Hartikainen
- A/Prof Simon Bell
Acknowledgements
- Geoff and Elaine Penney Ageing
Research Unit
- University of Sydney
- NHMRC
- NIA, NIH, USA
- Alzheimer’s Australia
Disclosures
- No financial conflicts of interest