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Polypharmacy and
medicines optimisation
Dr Martin Duerden
m.g.duerden@bangor.ac.uk
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Polypharmacy is not new!
We dislike polypharmacy as much as it is possible, and we
would never exhibit a remedy of any kind unless we had a
scientific reason for so doing and unless we were prepared
to defend our method of treatment.
W Newnham, Provincial Medical and Surgical Journal,
1848
Defining polypharmacy
• Appropriate polypharmacy is prescribing for
an individual for complex conditions or for
multiple conditions in circumstances where
medicines use has been optimised and the
medicines are prescribed according to best
evidence. The overall intent for the
combination of medicines prescribed should
be to maintain good quality of life, improve
longevity and minimise harm from drugs.
• Problematic polypharmacy is where
multiple medications are prescribed
inappropriately, or where the intended benefit
of the medication is not realised, or where
one or more of the following apply…
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Problematic….where one or more of the
following apply…
• The drug combination is hazardous because of
interactions.
• The overall demands of medicine-taking, or ‘pill burden’,
are unacceptable to the patient.
• These demands make it difficult to achieve clinically
useful medication adherence (reducing the ‘pill burden’
to the most essential medicines is likely to be more
beneficial).
• Medicines are being prescribed to treat the side effects
of other medicines where alternative solutions are
available to reduce the number of medicines prescribed.
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Defining medicines optimisation
NICE, Medicines Optimisation Guideline NG1, March 2015.
• A person-centred approach to safe and effective
medicines use, to ensure people obtain the best
possible outcomes from their medicines.
• Applies to people who may or may not take their
medicines effectively.
• Shared decision-making is an essential part of
evidence-based medicine, seeking to use the
best available evidence to guide decisions about
the care of the individual patient, taking into
account their needs, preferences and values.
“Social prescriptions”
• Exercise (on prescription)
• Arts (on prescription)
• Educational programmes
• Social contact for isolation and loneliness
• Links to voluntary organisations
• Community activities
• Alleviating boredom
• Consider alcohol problems
• etc.
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What’s the problem?
The growth of multimorbidity and
associated polypharmacy
(and guidelines and targets!)
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Estimated and projected age structure of the United Kingdom
population, mid-2014 and mid-2039 (Report, October 2015)
www.ons.gov.uk/ons/rel/npp/national-population-projections/2014-based-projections/index.html
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Percentage age distribution, UK, year ending mid-1971 to year
ending mid-2089 (Report, October 2015)
www.ons.gov.uk/ons/rel/npp/national-population-projections/2014-based-projections/index.html
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Number of chronic disorders by age group
Barnett K et al. Lancet 2012; 380: 37-43.
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Comorbidity of 10 common conditions among
UK primary care patients
Guthrie B et al. BMJ 2012;345:e6341
Prescribing is increasing
Guthrie et al. BMC Medicine (2015) 13:74
DOI 10.1186/s12916-015-0322-7
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Prevalence of
polypharmacy
in a Scottish
primary care
population.
Payne et al. Eur J Clin
Pharmacol 2014;
DOI 10.1007/s00228013-1639-9
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A nation of pill takers? Health Survey for England, 2013
Report 2015: www.hscic.gov.uk/catalogue/PUB16076
• 43% men and 50% women reported that they had taken at
least 1 prescribed medicine in the last week
• 22% men and 24% women reported that they had taken at
least 3 prescribed medicines in the last week
• More than 50% of participants aged 65-74 and more than 70%
of those aged >75 had taken at least 3 prescribed medicines.
• The most frequently reported prescribed medicine classes
were:
• lipid-lowering medicines – 16% men and 12% women
• antihypertensive medicines (14% and 15% respectively)
• for women, analgesics and/or NSAIDs (12%).
A nation of pill takers? Health Survey for England, 2013
Report 2015: www.hscic.gov.uk/catalogue/PUB16076
A nation of pill takers? Health Survey for England, 2013
Report 2015: www.hscic.gov.uk/catalogue/PUB16076
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Polypharmacy – identifying high risk
• A pragmatic approach to identifying
higher-risk polypharmacy in
practice is to focus on patients at
particularly high risk.
• For example:
• Those receiving 10 or more regular
medicines, or
• Those receiving 4 to 9 regular
medicines together with other
unfavourable factors (examples include:
a contraindicated drug; where there is
potential for drug-drug interaction; or
where medicine taking has proved a
problem in the past).
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Guidelines everywhere…
2008
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Prostate cancer
Osteoarthritis
Surgical management of OME
Irritable bowel syndrome
Antenatal care
Diabetes in pregnancy
Prophylaxis against infective
endocarditis
Perioperative hypothermia
(inadvertent)
Type 2 diabetes
Lipid modification
Stroke
Respiratory tract infections
Induction of labour
Familial hypercholesterolaemia
Attention deficit hyperactivity
disorder (ADHD)
Chronic kidney disease
Surgical site infection
Metastatic spinal cord
compression
2009
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Medicines adherence
Antisocial personality disorder
Borderline personality disorder
(BPD)
Rheumatoid arthritis
Breast cancer (early & locally
advanced)
Breast cancer (advanced)
Schizophrenia
Critical illness rehabilitation
Diarrhoea and vomiting in
children under 5
Glaucoma
Coeliac disease
Type 2 Diabetes - newer agents
Low back pain
When to suspect child
maltreatment
Depression in adults
Depression with a chronic
physical health problem
2010
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Venous thromboembolism reducing the risk
Donor breast milk banks
Unstable angina and NSTEMI
Chest pain of recent onset
Neuropathic pain pharmacological management
Lower urinary tract symptoms
Neonatal jaundice
Constipation in children and
young people
Alcohol-use disorders: physical
complications
Chronic obstructive pulmonary
disease
Bacterial meningitis and
meningococcal septicaemia
Delirium
Metastatic malignant disease of
unknown primary origin
Motor neurone disease - noninvasive ventilation
Barrett's oesophagus - ablative
therapy
Hypertension in pregnancy
Chronic heart failure
Transient loss of consciousness
in adults and young people
Pregnancy and complex social
factors
Nocturnal enuresis - the
management of bedwetting in
children and young people
Sedation in children and young
people
2011
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Anxiety
Anaemia management in people
with CKD
Alcohol dependence and harmful
alcohol use
Food allergy in children and
young people
Tuberculosis
Colonoscopic surveillance for
prevention of colorectal cancer
Diabetic foot problems - inpatient
management
Psychosis with coexisting
substance misuse
Lung cancer
Ovarian cancer
Common mental health disorders
Hip fracture
Peritoneal dialysis
Stable angina
Hypertension
Autism in children and young
people
Multiple pregnancy
Hyperglycaemia in acute
coronary syndromes
Colorectal cancer
Caesarean section
Self-harm (longer term
management)
Anaphylaxis
Organ donation
Service user experience in adult
mental health
2012
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Epilepsy
Patient experience in adult NHS
services
Infection control
Opioids in palliative care
Acute upper GI bleeding
Autism in adults
Sickle cell acute painful episode
Venous thromboembolic diseases
Spasticity in children and young
people
Osteoporosis fragility fracture
Lower limb peripheral arterial
disease
Urinary incontinence in
neurological disease
Antibiotics for early-onset
neonatal infection
Headaches
Neutropenic sepsis
Crohn’s disease
Psoriasis
Ectopic pregnancy and
miscarriage
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Potentially serious drug-drug interactions between drugs recommended by clinical
guidelines for three index conditions and drugs recommended by each of other 11 other
guidelines. Dumbreck et al. BMJ 2015;350:bmj.h949
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Guidelines also rarely tell us when to stop…
The challenge of ‘deprescribing’
(see WeMeReC Bulletin 2010 and eNotes, www.wemerec.org )
• Is the drug still needed?
• Has the condition changed?
• Can the patient continue to benefit?
• Has the evidence changed?
• Have the guidelines changed?
• Is the drug to treat an iatrogenic problem?
• What are the ethical issues about withholding care?
• Would discontinuation cause problems? – opioids,
antidepressants, BDPs/Z-drugs, corticosteroids, beta-blockers
etc.
• [+ Do ‘End of Life’ considerations apply? ]
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Pharmacology and older people
Milton et al. BMJ 2008;336:606-609.
• Reduction in renal clearance
• Reduction in liver size and metabolism, reduced albumin
• Reduction in lean body mass
• Increased pharmacodynamic/sensitivity to drugs – partic.
CNS
• Increased morbidity and co-morbidities
• Polypharmacy – risk of ADRs, interactions
• (+ FALLS!)
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Polypharmacy
Some key points (from the KF report)
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Key points – choosing to prescribe (KF)
• For many people, appropriate polypharmacy will
extend life expectancy and improve their quality
of life. Where there is no evidence of benefit from
the drugs being prescribed, polypharmacy should
be avoided.
• The evidence for choosing treatment where there
is polypharmacy should ideally be clearly stated.
Prescribers should record the rationale for nonevidence-based prescriptions, for example,
through patient choice.
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Key points – the patient perspective (KF)
• People often do not take medicines in the way
that prescribers intend and there is considerable
evidence that many dispensed medicines remain
unused or are wasted. These problems increase
as drug regimens become more complex.
• The patient perspective on medicine-taking
needs to be determined. Compromise may be
needed between the view of the prescriber and
the patient’s informed choice.
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Key points – evidence and guidelines (KF)
• Many clinical trials and practice guidelines do not consider
polypharmacy in the context of multi-morbidity. A singledisease framework prevails in most health care systems,
medical research and medical education.
• It is important that pragmatic clinical trials are conducted
that include patients with multi-morbidity and
polypharmacy.
• Guidelines should be developed that take account of longterm conditions that commonly co-exist, such as diabetes,
coronary heart disease, heart failure and chronic
obstructive pulmonary disease.
Lehman and Krumholz.
BMJ 2010;340:c580
– when QOF set at <7%
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The original “polypill” idea? The LODR
Salim Yusuf. Lancet 2002:360:2-3
Potential cumulative impact of four simple secondary-prevention
treatments:
Intervention
Relative-risk reduction
2-year event rate
..
8%
Aspirin
25%
6%
ß-blockers
25%
4·5%
Lipid lowering
30%
3.0%
25%
2.3%
No intervention
(by 1·5 mmol/L)
ACE inhibitors
Cumulative relative risk reduction if all four drugs are used is about 75%
But also….. smoking cessation, BP treatment, etc.…..
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OK – which 5?
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Medicalisation, too much medicine,
overdiagnosis, Prudent Healthcare, and
Choosing Wisely
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Key points – training, organisation (KF)
• Multimorbidity and polypharmacy increase clinical workload.
Doctors, nurses and pharmacists need to work coherently as a
team, with a carefully balanced clinical skill-mix.
• There should be more training in managing complex multimorbidity, polypharmacy and other aspects of medicines
management.
• This could include GPs, clinicians who specialise in care of
older people, orthogeriatricians, clinical pharmacologists, nurse
specialists and clinical pharmacists.
• Patients with multi-morbidity admitted to hospital under one
specialty may require access to a generalist clinician to coordinate their overall care.
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Key points – adverse effects (KF)
• Prescribers may not recognise that symptoms could be
iatrogenic and unwittingly prescribe new medication to
counter the adverse effects of other drugs. This is known
as incremental prescribing or the ‘prescribing cascade’
and should be avoided.
• Prescribers should consider whether interactions between
drugs where medication is combined will undermine
therapeutic benefit.
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Key points – end of life (KF)
• Many people stay on medicines beyond the point where
they are deriving optimal benefit from an intervention.
When reviewing medications, health care professionals
should consider if treatment can be stopped and
recognise that ‘end-of-life’ considerations apply to many
chronic diseases as well as cancer-related conditions.
www.goldstandardsframework.org.uk
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Teams, prescribing systems
…and place of decision support
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Clinical pharmacists in the team
• Reviewing systems – repeat prescriptions, drug
monitoring protocols, response to hazard/warnings
• Significant event reviews, audits
• Identifying and targeting those:
• on high risk drugs
• at risk (polypharmacy, multimorbidity, frail etc.)
• on inappropriate/unsafe drugs
• Post discharge and reconciliation reviews
• Support to care homes
• Medication reviews – medicines optimisation
• Case management
• Supporting Reducing Unplanned Admission Enhanced
Service (or equivalent)
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The PINCER trial
Avery A, et al. Lancet 2012; 379:310-319
• The study involved at-risk patients who were being prescribed drugs
that are commonly and consistently associated with medication errors
• 72 practices, cluster randomisation: Simple feedback - Computergenerated feedback on patients at potential risk from hazardous
prescribing (n=36) vs. Pharmacist-led intervention, simple feedback
plus educational outreach and dedicated support to correct and
prevent potentially hazardous prescribing (n=36)
• At 6-months follow-up patients in the PINCER group were:
• 42% less likely to have been prescribed a non-selective NSAID if they had a
history of peptic ulcer without gastroprotection
• 27% less likely to be given a beta blocker if they had asthma
• Almost 50% less likely to be prescribed an ACE inhibitor or loop diuretic
without appropriate monitoring
= Using GP computer systems to identify patients at risk, combined with
a pharmacist intervention, can substantially reduce medication errors
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(Un)Safety Indicators: PINCER Query Library
www.nottingham.ac.uk/primis/tools-audits/list-of-audit-tools/pincer.aspx
Query 1: Patients with a history of peptic ulcer who have been prescribed a
non-selective NSAID without co-prescription of a PPI
Query 2: Patients with a history of asthma who have been prescribed a βblocker
Query 3: Patients aged 75 years and older who have been prescribed an ACEI
or a loop diuretic long-term who have not had a computer-recorded check of
their U&E in the previous 15 months
Query 4: Women with a past medical history of venous or arterial thrombosis
who have been prescribed combined hormonal contraceptives (CHC)
Query 5: Patients receiving methotrexate for at least three months who have
not had a recorded FBC or LFT within the previous three months
Query 6: Patients receiving warfarin for at least three months who have not
had a recorded check of their INR within the previous 12 weeks
Query 7: Patients receiving lithium for at least three months who have not had
a recorded check of their lithium concentrations in the previous three months
Query 8: Patients receiving amiodarone for at least six months who have not
had a TFT within the previous six months
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Much to be done – variation in prescribing safety
Stocks et al. BMJ 2015;351:h5501 (see December KINES)
• 526 practices across the UK contributing to CPRD up to April 2013.
• Anonymised data from patients >18yrs, database of 5 million.
• Analysed using indicators developed from PINCER.
• 49,927 of the 949,552 patients at risk triggered at least one
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prescribing indicator – 5.26% (95% CI 5.21% to 5.30%).
21,501 of 182,721 – 11.8% (95% CI 11.6% to 11.9%) triggered at
least one monitoring indicator.
The prevalence of potential prescribing hazard ranged from 0 to
10.2%, and for inadequate monitoring ranged from 10.4% to 41.9% =
substantial variation.
Older patients and those prescribed multiple repeat medications
had significantly higher risks of triggering a prescribing indicator.
Younger patients with fewer repeat prescriptions had significantly
higher risk of triggering a monitoring indicator.
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STOPP (Screening Tool of Older Person's Prescriptions) and
START (Screening Tool to Alert doctors to Right Treatment)
www.ucc.ie/en/misl/research/previous/stopp_start
• Developed in Cork, Ireland
• Delphi Questionnaire – 18 experts, first published 2008
• Widely researched and adopted since then
• Version 2 published October 2014, updated with wider
European-wide consensus
• 87 STOPP rules
• 34 START rules
• Applies to people >65 years
• Distinction from PINCER is that represent indicators of
potentially inappropriate prescribing, rather than
focused purely on (un)safety
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STOPP: Some CVS Examples
• Digoxin at a long-term dose > 125μg/day with impaired
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renal function
Loop diuretic for dependent ankle oedema only i.e. no
clinical signs of heart failure
Loop diuretic as first-line monotherapy for hypertension
Thiazide diuretic with a history of gout
Non-cardioselective beta-blocker with COPD
Beta-blocker in combination with verapamil
Calcium channel blockers with chronic constipation
Aspirin at dose > 150mg day
Aspirin with no history of coronary, cerebral or peripheral
vascular symptoms or occlusive event
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START: Some CVS Examples
• Aspirin or clopidogrel with a history of atherosclerotic
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coronary, cerebral or peripheral vascular disease in
patients with sinus rhythm
Antihypertensive therapy where systolic BP consistently
>160 mmHg
Statin therapy with a history of coronary, cerebral or
peripheral vascular disease, where functional status
remains independent for activities of daily living and life
expectancy is > 5 years
Angiotensin Converting Enzyme (ACE) inhibitor with
chronic heart failure
ACE inhibitor following acute myocardial infarction
Beta-blocker with chronic stable angina
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By way of conclusion….
Resources and challenges
www.awmsg.org/medman_library.html
www.sehd.scot.nhs.uk/dl/DL(2015)04.pdf
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Medicines optimisation and polypharmacy
Many challenges, including….
• Time, resources, manpower – doctors, nurses, pharmacists
• Importance of formal medication review
• Multidisciplinary assessment (vs. specialism)
• ‘One-stop shop’ reviews
• Getting evidence of improved patient outcome
• Shared decision-making (and recording)
• Coding accuracy for decision support
• Adaptive guidelines
• Alert fatigue
• Use of “order sentences” & stating what medication is for
• Interfaces, and integrated care; care homes