University of Dundee School of Medicine

Optimising prescribing in primary

care in the face of multimorbidity

and polypharmacy

Bruce Guthrie

Professor of Primary Care Medicine, University of Dundee

NICE Multimorbidity Guideline Development Group Chair

The limits of current evidence• Exclusion criteria driving this pattern

– Age, comorbidity, co-prescription

– ‘Investigator discretion’ and many others on top

• Median exclusion for common conditions– Atrial fibrillation 38%, CHD 75%, hypertension 83%,

COPD 84%, rheumatoid arthritis 92%, type 2 diabetes 93%, asthma 96%

Die of disease

Precision 1

Die of ‘stuff’

Precision 2

http://geriatricresearch.medicine.dal.ca/pdf/Clinical%20Faily%20Scale.pdf

High-risk prescribing• Prescribing is a high benefit, high risk, high cost activity

• 6.5% of hospital admissions are related to ADEs

– ADE directly leading to admission in 80%, half preventable

• Mostly due to ‘appropriate’ drugs that guidelines tell us to prescribe more of

– Warfarin, aspirin, (non-steroidal anti-inflammatory drugs), ACEI/ARB and other renal toxic drugs, hypoglycaemic drugs, blood pressure lowering drugs

• High-risk or potentially inappropriate prescribing is not a never event, but needs regular review

– The correct level is NOT zero

High risk prescribing – variation between practices

Guthrie B et al. BMJ 2011;342:d3514

0

0.5

1

1.5

2

2.5

3

3.5

Odd

s ra

tio

of p

atie

nt r

ecei

ving

a h

igh

risk

pre

scri

ptio

n in

ea

ch p

ract

ice

Practices ranked in ascending order of prevalence of high risk prescribing

Odds ratio for each practice

Upper 95% CI

Lower 95% CI

High risk prescribing – variation between patients

Guthrie B et al. BMJ 2011;342:d3514

No. of chronic drugs

% getting a high risk prescription

Adjusted OR

0 drugs1-2 drugs3-4 drugs5-6 drugs7-8 drugs

9-10 drugs11+ drugs

4.311.012.714.518.321.526.6

Reference2.73.23.85.06.17.9

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80+

Per

cen

tage

of

pat

ien

ts r

ece

ivin

g sp

ecif

ied

nu

mb

er o

f d

rugs

Age group

No. of drug classes dispensed in last 84 days in 1995

0 drugs

1 drug

2 drugs

3 drugs

4 drugs

5 drugs

6 drugs

7 drugs

8 drugs

9 drugs

10 drugs

11 drugs

12 drugs

13 drugs

14 drugs

15+ drugs

Guthrie B et al. BMC Medicine 2015

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80+

Per

cen

tage

of

pat

ien

ts r

ece

ivin

g sp

ecif

ied

nu

mb

er o

f d

rugs

Age group

No. of drug classes dispensed in last 84 days in 1995

0 drugs

1 drug

2 drugs

3 drugs

4 drugs

5 drugs

6 drugs

7 drugs

8 drugs

9 drugs

10 drugs

11 drugs

12 drugs

13 drugs

14 drugs

15+ drugs0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80+

Per

cen

tage

of

pat

ien

ts r

ece

ivin

g sp

ecif

ied

nu

mb

er o

f d

rugs

Age group

No. of drug classes dispensed in last 84 days in 2010

0 drugs

1 drug

2 drugs

3 drugs

4 drugs

5 drugs

6 drugs

7 drugs

8 drugs

9 drugs

10 drugs

11 drugs

12 drugs

13 drugs

14 drugs

15+ drugs

Guthrie B et al. BMC Medicine 2015

Safer but more people at risk…

• People on warfarin prescribed NSAIDs, anti-platelets, high-risk antibiotics, oral azole antifungals

• 16.0% in 1995 (258/1611)

• 10.7% in 2010 (538/5006)

• ‘Safer’ but more people are at risk…

• Even if increasing prescribing is more effective, it creates increasing risk that needs managing

Improving prescribing safety• Focus on indicators of high-risk prescribing

– Many available indicators of varying specificity

• Focus on people at particular risk

– Most commonly people with polypharmacy

• Focus on prescribing systems

– Medicines reconciliation at transitions

– Repeat prescribing systems

• Do something…

– Small things matter

Indicator interventions• PINCER (two arm cluster RCT in 72 practices)

– Pharmacist-led, some feedback, education & coaching

– ~40% reduction in targeted prescribing but effect wanes somewhat after the pharmacist leaves

• EFIPPS (three arm cluster RCT in 262 practices)

– Feedback +/- behaviour change intervention

– Six high-risk prescribing indicators

• DQIP (stepped-wedge cluster RCT in 33 practices)

– Educational outreach, informatics and financial incentives

– Nine high-risk prescribing indicatorsPINCER main trial paper. Avery et al. The Lancet 2012; 379(9823): 1310-9.

EFIPPS development. Barnett et al. Implementation Science 2014; 9(1):133.

DQIP development. Grant et al. BMJ Open 2014;4(1):e004153.

Guthrie et al. BMJ 2017:354; i4079

Avoid incident

high-risk prescribing

InformaticsEducationFinancial incentive

£15/patient reviewed

£350 up front

Outreach by pharmacist

Written educational

material

Progress updates

Patient identification

Facilitate review

Monitor progress

Review and correct prevalent

high-risk prescribing

DQIP intervention: Components

Dreischulte et al. NEJM 2016; 374: 1053-64.

DQIP trial findings

• Primary outcome 37% decrease

• ‘Ongoing’ high-risk prescribing 40% decrease

• ‘New’ high-risk prescribing 23% decrease

• Sustained 12 months after the intervention stopped

• Gastrointestinal bleeding admissions 34% decrease

• Heart failure admissions 27% decrease

• Acute kidney injury admissions 16% decrease (ns)

• Unrelated ACSA no changeDreischulte et al. NEJM 2016; 374: 1053-64.

Does it work in real life?

YES IT DOES! NO IT DOESN’T!

MacBride-Stewart et al. BJGP 2017:67;e352-e360.

“Triple whammy” Antipsychotics in dementia

Does it work in real life?

• No magic bullets

• The prescribing context matters

– Attribution and responsibility

– Fear of adverse consequences of stopping

– Professional culture rather than technical problem

• The organisational context matters

– Pharmacist-led concerns about sustainability

– GP-led may alter future prescribing more

Polypharmacy interventions• Cochrane review (12 studies)

– Some evidence for improved prescribing outcomes, little evidence for change in clinical outcomes

• National guidance – http://www.polypharmacy.scot.nhs.uk/

– http://www.sehd.scot.nhs.uk/publications/DC20150415polypharmacy.pdf

• Part of GP contract

– In the process of major change

• Increasing use of primary care pharmacists

– Various roles including polypharmacy review

• Aim to use informatics to support reviewhttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008165.pub3/full

NHS Scotland polypharmacy

NHS Scotland 7 step review process1. Identify the goals of therapy – what are we trying to achieve?

2. Identify essential drug therapy

3. Does the patient take unnecessary drug therapy?

4. Are therapeutic objectives being achieved?

5. Does the patient have, or is at risk of, adverse drug reactions?

6. Is there a significantly cheaper alternative?

7. Is the patient willing & able to take drug therapy as intended?

http://www.polypharmacy.scot.nhs.uk/

Past medical history• Hypothyroidism

• Urinary urgency

• Hypertension

• Diabetes

• Intermittent knee pain

• Possible TIA (funny turn/fall –> “treat as TIA”)

• Hip fracture after a fall

• Independent and manages well, long-term memory excellent

What’s the right drug treatment?• Thyroxine 75mcg od• Solifenacin 10mg od• Perindopril 4mg od• Indapamide 2.5mg od• Bisoprolol 5mg od• Atorvastatin 40mg nocte• Metformin 500mg tds• Gliclazide 80mg bd• Clopidogrel 75mg od• Naproxen 500mg as needed• Calcium and vit D3 1 tab bd• Alendronate 70mg weekly

• Hypothyroidism (TFTs fine)

• Urinary frequency

• Hypertension (BP 136/72)

• Diabetes (HBA1c 50, cholesterol 3.3, no microvascular complications)

• Intermittent knee pain

• Possible TIA

• Hip fracture after a fall

Functional status

• “Independent and manages well”– Walks the dog several miles a day, does the

shopping for all the neighbours

– Lives alone but twice daily carers and family visit daily, uses a dispensing aid, “walking frame fantastic”

• “Long term memory excellent”– Cognitive impairment or dementia

What’s the right drug treatment?• Thyroxine 75mcg od• Solifenacin 10mg od• Perindopril 4mg od• Indapamide 2.5mg od• Bisoprolol 5mg od• Atorvastatin 40mg nocte• Metformin 500mg tds• Gliclazide 80mg bd• Clopidogrel 75mg od• Naproxen 500mg as needed• Calcium and vit D3 1 tab bd• Alendronate 70mg weekly

1. Identify the goals of drug therapy – what are we trying to achieve?

2. Identify essential drug therapy

3. Does the patient take unnecessary drug therapy?

4. Are therapeutic objectives being achieved?

5. Does the patient have adverse drug reactions, or is at risk of ADRs?

6. Is there a significantly cheaper alternative?

7. Is the patient willing and able to take drug therapy as intended?

• What are we trying to achieve?

– Patient/carer

– Clinician

• Patient context

– Life expectancy

– Frailty

• Quality of life and/or longer term prevention

120 indicators• High risk prescribing

• Potential over-treatment

• Omitted monitoring

• Potential under-treatment

Polypharmacy interventions• Needs much more than an informatics tool

– Evidence for treatment effectiveness in this population

– Professional practices don’t always align

– Patient/carer expectations don’t always align

– Time and resources

– What kind of professional or team?

• Culture

– Which life saving drug will I stop today?

– Difficult conversations about life, death and futility

Conclusion• Prescribing safety can be improved by

focusing on key indicators

• Optimising prescribing in polypharmacy is a hard nut to crack (but crack it we must)

– What are we trying to achieve here?

– Who is responsible? Should it be me?

• We really don’t understand our safety critical prescribing systems very well…

Want to do something?• High-risk drugs and indicators

– Insulin, warfarin, NSAIDs

– STOPP and START criteria

• Risk of AKI when dehydrated– Old, frail, CKD, heart failure

– On ACEI, ARB, diuretics, NSAIDs, metformin

• Can I stop a drug today?– Perfect risk factor control in the frail

– Drugs for symptoms which are no longer present

Want to do something?• Why do patients get high INRs? In my practice:

– Because they have chaotic control

– D&V/gastrointestinal upset

– Because we give them the wrong antibiotic

• Are some people unsafe on warfarin?

– Small number of people have chaotic INRs (6 patients in my practice had >200 INRs in a year)

• Direct oral anticoagulants

– Doesn’t fix non-adherence and dose is often wrong…

Want to do something?

• Let your imagination run riot but go and do something now…

Thank you

This presentation draws on work done in collaboration with many people

Tobias Dreischulte, Aileen Grant, Adrian Hapca, Karen Barnett, Chris Roberston, Marion Bennie, Kim Kavanagh, Lyall Cameron, Graham Longair, Sean Macbride-Stewart, Davy He, Dan Morales

NHS Scotland polypharmacy guidance

http://www.polypharmacy.scot.nhs.uk/

http://www.sehd.scot.nhs.uk/publications/DC20150415polypharmacy.pdf

NICE multimorbidity and medicines optimisation guidance

Multimorbidity https://www.nice.org.uk/guidance/ng56

Medicines Optimisation https://www.nice.org.uk/guidance/ng5