Time to Reduce the Implementation Gaps: The role of PCSK9i in - - PowerPoint PPT Presentation

Time to Reduce the Implementation Gaps: The role of PCSK9i in routine Clinical Practice

• Kausik K Ray
• President Elect European Atherosclerosis Society
• NIHR ARC National Lead for CVD
• Chief Clinical Officer and Trials Lead DISCOVER NOW, HDR UK Innovation Hub NW London
• Professor of Public Health and Consultant Cardiologist
• Director of the Imperial Centre for Cardiovascular Disease Prevention
• Deputy Director of the Imperial Clinical Trials Unit and Head of Commercial Trials, Imperial

College London

Disclosures

• Consultancy honoraria:

– AbbVie – Amgen – Cerenis Therapeutics – Eli Lilly and Company – Ionis Pharmaceuticals – Medco Health Solutions – Resverlogix – Sanofi-Regeneron – Astra Zeneca

• Professor of Public Health,

Imperial College London

• Research grant support:

– Amgen – Pfizer – MSD – Sanofi-Regeneron

• Speakers Bureau participation with:

– Algorithme Pharma – AstraZeneca – Boehringer Ingelheim – Cipla – Kowa Pharmaceuticals – Pfizer – Takeda Pharmaceuticals – Sanofi-Regeneron – Amgen – Dr Reddys

• To understand the role of LDL-C lowering in Guidelines
• To understand the basis of the lower LDL-C lowering in clinical practice
• To understand how lipid lowering treatments are used and the impact of health

and disease outcomes

• To assess implementation gaps and how these may be overcome

Objectives

2016 LDL-C goals1 2019 LDL-C goals2 Low risk < 3.0 mmol/L (116 mg/dL) Moderate risk < 3.0 mmol/L < 2.6 mmol/L High risk 50% reduction OR < 2.6 mmol/L 50% reduction AND < 1.8 mmol/L Very high risk 50% reduction OR < 1.8 mmol/L 50% reduction AND < 1.4 mmol/L Second CV event within 2 years NA* 50% reduction AND < 1.0 mmol/L

*Not applicable, extreme high risk patients did not have a specific LDL-C goal in the 2016 guidelines

CV, cardiovascular; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; LDL-C, low-density lipoprotein cholesterol; NA, not applicable. 1. Catapano AL, et al. Eur Heart J 2016; 37: 2999-3058. 2. Mach F, et al. Eur Heart J 2019; 41: 111-188

2016 and 2019 ESC/EAS ri risk-based LD LDL-C goals

Those wit ith hig ighest glo lobal ris isk k of CVD benefit it more from greater reductions in in LDL-C C

LDL-C reduction (mmol/L) with statin treatment LDL-C reduction (mmol/L) with statin treatment 5-year risk

• f major

vascular event 5-year risk

• f major

vascular event Vascular deaths avoided per 1000 Major vascular events avoided per 1000

Major vascular events avoided Vascular deaths avoided

Population Burden of f Non-Adherence and Under-treatment

Khunti KK, ……….Ray KK JAMA Network Open 2019

Population Burden of f Non-Adherence and Under-treatment

Khunti KK, ……….Ray KK JAMA Network Open 2019

Population Burden of f Non-Adherence and Under-treatment

Khunti KK, ……….Ray KK JAMA Network Open 2019

PURE study, 17 countries

26 24 25 20 9 17 20 19 20 14 15 14 43 40 42 13 14 13 17 9 15 20 40 60 80 100 CHD Stroke CHD or stroke Antiplatelet Beta-blockers ACEi or ARBs Diuretics BP-lowering Ca-channel blockers Statins

PURE, Prospective Urban Rural Epidemiology; ACEi, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; BP, blood pressure

Yusuf S et al. Lancet 2011;378:1231–1243

Overall l rates of f secondary prevention medication use for CVD is is lo low worldwide

% of patients with treatment

Overall LL LLT use & ri risk-based LD LDL-C goal attainment in in Europe

52 28 9 6 4 1

20 40 60 80 100 Moderate intensity statin monotherapy High intensity statin monotherapy Ezetimibe combination Other LLT Low intensity statin monotherapy PCSK9i combination

% of patients receiving stabalised LLT *

LLT use at LDL-C measurement

54 33

20 40 60 80 100

2016 LDL-C goal 2019 LDL-C goal

% of patients achieving their risk-based L;DL-C goal

• The majority of patients did not achieve their

2016 risk-based goal

• Only one-third achieved their 2019 goal

*Stabilised LLT at time of LDL-C measurement. LLT, lipid lowering therapy

• The majority of patients were receiving moderate

intensity statin monotherapy

• Only 28% were receiving high intensity statin
• Few (9%) were receiving ezetimibe

Compared to historical management

• Greater use of moderate intensity statin monotherapy
• By definition this means that patients achieve 30-50% LDL-C lowering
• But if absolute residual risk is high then even 30-50% LDL-C reduction

may not be enough

LD LDL-C le levels and th those on stable Li Lipid Lo Lowering Treatments

2,40 2,02

0,0 0,5 1,0 1,5 2,0 2,5

Primary Prevention (n=2558) Established ASCVD (n=2039)* Mean (SE) stabilised LDL-C levels (mmol/L)

2,31 2,18

0,0 0,5 1,0 1,5 2,0 2,5

Moderate intensity statin monotherapy (n=2131) High intensity statin monotherapy (n=1134) Mean (SE) stabilised LDL-C levels (mmol/L)

*Includes patients with cerebral, coronary or peripheral disease. ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; LLT, lipid lowering therapy; SE, standard error

Ezetimibe added to optimised statin ins gets you to 2016 goals ls NOT 2019 goals. This is is is achie ieved wit ith Mabs plu lus LLT

2,3 2,16 1,62 0,8 1,08 0,5 1 1,5 2 2,5 Moderate High high plus Eze Plus Mabs

On treatment LDL-C levels if we intensify LDL-C lowering (add on Tx)

Series 3 Series 4

LDL-C

Observ rved LD LDL-C goal attainment by LL LLT in in secondary ry prevention

2,3 43,5 37,5 9,3 1,1 6,3

LLT use

Low intensity statin mono (n=47) Moderate intensity statin mono (n=887) High intensity statin mono (n=764) Ezetimibe combo (n=189) PCSK9i (n=24) Other LLT (n=128)

Figures show % of patients receiving each LLT and % achieving 2016 (solid bars) and 2019 (hashed bars) LDL-C goals. combo, combination; LLT, lipid lowering therapy; mono, monotherapy.

8 58 21 22 16 13 18 15 67 54 45 36 19 30

2016/2019 goal attainment

Overall (n=2039)

Real world use of PCSK 9 Mab- as per local guidelines and reimbursement in Europe

Assess risk and titrate to risk Here is how

The Role of f PCSK9 Mabs in New Guidelines

Baseline LDL-C and magnitude of f LDL-C C reduction needed to achieve goals

Conclusions

• Guidelines advocate first Optimise Statins (High Intensity)
• BUT even when optimized LDL-C > 2mmol/L
• Adding Ezetimibe based on starting levels helps to achieve old 2016

goals

• PCSK9 inhibitors in addition to oral LLT are needed if the new 2014

LDL-C goals of <1.4mmol/L are to be acheieved

• Greater use of combination therapy will be needed in Europe as

currently < 1:5 will achieve an LDL-C of < 1.4mmol/L

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