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 › What is the problem?

Medicines not helping achieve aims?

Medicines causing harm?

Cost of medicines?

› According to who?

Patients/caregivers Clinicians Researchers Policy makers › 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

Growing and highly variable Ageing Population 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 Incontinence Functional decline Confusion 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

› Evidence-based practice What do clinicians want?

› Ethical practice Beneficence Non-maleficence Autonomy www.zazzle.com

healthwise-everythinghealth.blogspot.com

10

National Medicines Policy What do policy makers want?

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 Prevention Disease Management Geriatric syndromes Maintain Function Last year of life 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 18

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

20

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, non frail 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) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Frail Admission Frail Discharge Frail (n = 140) Not Frail Admission Not Frail Discharge Not Frail (n = 80) None Aspirin/Other Warfarin 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

A bsorption D istribution M etabolism E xcretion

Ageing

↔ ↓water ↑fat ↓albumin ↓ phase 1 ? phase 2 ↓

Frailty

?

↓↓water ↑↑fat ↓↓ albumin ?↓ phase 1 ↓ phase 2 ↓↓ 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.

31

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

32

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 33

Interactive Concentric Model of Geriatric Syndromes: Example of falls Autonomic Degeneration Risk Factor Synergism Anti-hypertensives 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 Impaired Cognitive Function

Falls Risk Increasing Drugs CNS Medicines Sedative Load Anticholinergic Burden Drug Burden Index x x x x x x x x x x 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 Falls Community dwelling, USA, Community dwelling men, Australia Community dwelling, Finland Inpatients, UK Residential aged care, Australia Hospitalisation Mortality Frailty Inpatients, UK Community dwelling, Finland War Veterans, Australia Community dwelling, Finland 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.

39

› 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