Professor Chris BullenPublic Health Physician and Health Researcher

Director of the National Institute for Health

Innovation

Professor of Public Health

The University of Auckland

8:15 - 9:10 WS #192: The Place of the Polypill in Managing Cardiovascular Risk

9:20 - 10:15 WS #204: The Place of the Polypill in Managing Cardiovascular Risk (Repeated)

The Place of the Polypill

in Managing Cardiovascular

Risk

Chris BullenThe University of

Auckland

What is the CVD polypill?

Do polypills actually work?

Should I prescribe

them - and if so, how & for

whom?

2011-12 2015-16

NZ CVD Risk Management Guidelines 2013

“Most patients with a combined CVD risk over about 20% in 5 years and all patients with a personal history of CVD are likely to benefit significantly from both BP- and lipid-lowering drugs and antiplatelet drugs, over and above intensive non-pharmacological interventions.”

CVD risk management c2008

78% at high CVD risk on BP lowering drugs, 72% on lipid lowering drugs, 65% on anti-platelet drugs but only 50% were prescribed all three treatments.

Among those with either diabetes or established CVD, only 34% were meeting BP or lipid management recommendations.

Peiris D, Murray J, Scully D, et al. NZ Med J 2008;121(1285).

CVD risk management c2012

81% dispensed BP lowering medications and 73% lipid-lowering medications

Only 67% were receiving both.

Mehta S, Wells S, Grey C, et al. Eur J Prev Card 2014;21:192-202.

The CVD polypill

Wald N, Law M. A Strategy to reduce cardiovascular disease by more than 80%. BMJ 2003

“…a greater impact on the prevention of disease in the Western world than

any other known intervention”

Guglietta, M. Guerrero. Nat Clin Pract Cardiovasc Med, 6 (2009)

Name Company Components (mg)

RHP 1 Dr Reddys Aspirin 75, atenolol 50, lisinopril 10,simvastatin 20

RHP2 Dr Reddys Aspirin 75, HCT 12.5, lisinopril 10, simvastatin 20

Polycap Cadila Aspirin 100, Atenolol 50, HCT 12.5, ramipril 5, simvastatin 20

PolycapDS

Cadila Atenolol 100, HCT 25, ramipril 10, simvastatin 40

Polypill Cipla amlodipine 2.5, losartan 25, hydrochlorothiazide 12.5, simvastatin 40

Zycad-4 Zydus Cadila Aspirin 75, atorvastatin 10, metoprolol 50, ramipril 5

Ramitorva Zydus-Cadila Aspirin 75, atorvastatin 10, ramipril 5

Polytorva USV Aspirin 75, atorvastatin 5, ramipril 10

PolyIran 1 Alborz Darou Aspirin 81, atorvastatin 20, enalapril 5, HCT 25

PolyIran 2 Alborz Darou Aspirin 81, atorvastatin 20, HCT 25, valsartan 40

Polypill Hypermarcas Atorvastatin 10, lisinopril 50, HCT 12.5

Trinomia Ferrer Aspirin 100, ramipril 2.5/5/10, simvastatin 40

Sanz & Fuster, 2013

Do polypills actually work?

Do they improve adherence?

Do they improve BP and lipids?

Do they reduce CVD events and mortality?

Open label RCT n=513 (50% Māori), from 54 GPs, 2010-13

PP vs usual care from usual GP, 12 months f/up

RHP 1: Aspirin 75mg, atenolol 50mg, lisinopril 10mg, simvastatin 20mg

RHP 2: Aspirin 75mg, HCT 12.5mg, lisinopril 10mg, simvastatin 20mg

Selak et al BMJ 2014

Adherence to all 4 Rx increased by 75% - PP group (81%) vs

usual care (46%)

Change in RFs small at 12 months but in meta-analysis with other PP

trials SBP declined by -2 mmHg and LDL C by 0.1 mmol/L

Selak et al BMJ 2014

Other Polypill Trials

• Adherence improvements

• Risk factor reductions –but not as much as Wald and Law estimated

The benefits of combination low-dose treatment

Half standard dose

Reduction in DBP

Reduction in CHD

Reduction in Stroke

1 drug 3.7mmHg 19% 29%

2 drugs 7.3mmHg 34% 49%

3 drugs 10.7mmHg 46% 63%

Observed and expected reduction in BP and LDL cholesterol on the CVD Polypill.

Wald DS, Morris JK, Wald NJ (2012) Randomized Polypill Crossover Trial in People Aged 50 and Over. PLoS ONE 7(7): e41297. http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0041297

CVD events & mortality

Systematic review and meta-analysis 1996-2015, 123 studies, n=613,815

• Every 10 mmHg reduction in SBP reduced risk of CVD events by 20%, CHD by 17%, stroke 27% and HF 28%]

• 13% reduction in all-cause mortality

Ettehad et al. Lancet 2016

CVD events & mortality

Two placebo-controlled end–point trials underway:

–Stroke and TIA

–MI in patients aged 65+ with an MI

What would you include in a Polypill if you were designing

one?

Turn to a few people around you and take the next few minutes to come up

with an answer

Should I prescribe them?

Who for?

•Patients who are at high CVD risk and non-adherent to current medications

• Everyone over 50???

Availability?

•PPs approved for use in 22 countries

• Not in NZ yet

Affordability?

How to prescribe a polypill

Once a day pill/capsule

Part of a wider intervention package including smoking cessation, weight management etc.

Stop existing therapy and start PP.

For patients not on equivalent doses of BP lowering medications, start with smaller doses of individual components then titrate up as tolerated before PP is started.

Concerns

What concerns do you or others have about polypills for secondary prevention of CVD?

Turn to a few people around you and take the next few minutes to identify some concerns

Concerns

Medicalise healthy people

Antithesis of personalised

medicine

Encourage non-

adherence to non-drug

interventions

Widening of ethnic

disparities

What we found

• Adherence to lifestyle risks– IPDM of n=3140 high-risk patients in 6 countries– No difference in lifestyle RFs (BMI, MIPA and smoking) between PP and usual

care over 15 months

• Ethnic disparities– PP use led to increase in use of recommended medication among Maori (by

87%) and non-Maori (by 66%) at 12 months compared with usual care,

• Adverse effects– Equivalent in both IMPACT arms but low BP & bleeding events higher in PP

group– 30% discontinued PP by 12 months

• Costs

Selak et al, Prev Cardiol 2016; Selak et al BMJ 2014

Take Homes

• Polypills are coming - for secondary prevention, and perhaps primary prevention, of CVD

• Relatively few harms

• They improve adherence especially in poorly adherent patients

• They show benefits for BP and cholesterol, almost certainly reduce risk of events and mortality