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 • • Professor of Public Health, Research grant support: Imperial College London – Amgen – Pfizer • Consultancy honoraria: – MSD – AbbVie – Sanofi-Regeneron – Amgen • Speakers Bureau participation with: – Cerenis Therapeutics – Algorithme Pharma – Eli Lilly and Company – – AstraZeneca Ionis Pharmaceuticals – – Boehringer Ingelheim Medco Health Solutions – – Cipla Resverlogix – Kowa Pharmaceuticals – Sanofi-Regeneron – Pfizer – Astra Zeneca – Takeda Pharmaceuticals – Sanofi-Regeneron – Amgen – Dr Reddys

Objectives • 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

2016 and 2019 ESC/EAS ri risk-based LD LDL-C goals 2016 LDL-C goals 1 2019 LDL-C goals 2 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

Those wit ith hig ighest glo lobal ris isk k of CVD benefit it more from greater reductions in in LDL-C C Major vascular events avoided Vascular deaths avoided Major vascular events avoided per 1000 Vascular deaths avoided per 1000 5-year risk 5-year risk of major of major vascular vascular event event LDL-C reduction (mmol/L) with statin treatment LDL-C reduction (mmol/L) with statin treatment

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

Overall l rates of f secondary prevention medication use for CVD is is low worldwide lo PURE study, 17 countries 100 Antiplatelet Beta-blockers ACEi or ARBs Diuretics BP-lowering Ca-channel blockers Statins % of patients with treatment 80 60 43 42 40 40 26 25 24 20 20 20 19 17 17 15 15 20 14 14 14 13 13 9 9 0 CHD Stroke CHD or stroke 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 LL LLT use & ri risk-based LD LDL-C goal attainment in in Europe • The majority of patients were receiving moderate 100 100 • The majority of patients did not achieve their LLT use at LDL-C measurement intensity statin monotherapy % of patients achieving their risk-based L;DL-C goal 2016 risk-based goal • Only 28% were receiving high intensity statin % of patients receiving stabalised LLT * • Only one-third achieved their 2019 goal • Few (9%) were receiving ezetimibe 80 80 60 60 54 52 40 40 33 28 20 20 9 6 4 1 0 0 Moderate High intensity Ezetimibe Other LLT Low intensity PCSK9i 2016 LDL-C goal 2019 LDL-C goal intensity statin combination statin combination statin monotherapy monotherapy monotherapy *Stabilised LLT at time of LDL-C measurement. LLT, lipid lowering therapy

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

LDL-C le LD levels and th those on stable Li Lipid Lo Lowering Treatments 2,5 2,5 2,40 Mean (SE) stabilised LDL-C levels (mmol/L) 2,31 Mean (SE) stabilised LDL-C levels (mmol/L) 2,18 2,0 2,0 2,02 1,5 1,5 1,0 1,0 0,5 0,5 0,0 0,0 Moderate intensity statin High intensity statin Primary Prevention (n=2558) Established ASCVD (n=2039)* monotherapy (n=2131) monotherapy (n=1134) *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 On treatment LDL-C levels if we intensify LDL-C lowering (add on Tx) 2,5 2,3 2,16 2 1,62 1,5 LDL-C 1,08 1 0,8 0,5 0 Moderate High high plus Eze Plus Mabs Series 3 Series 4

Observ rved LD LDL-C goal attainment by LL LLT in in secondary ry prevention 2016/2019 goal attainment LLT use 30 Overall 2,3 (n=2039) 18 1,1 6,3 Low intensity 19 statin mono 13 (n=47) 9,3 Moderate 36 intensity statin mono (n=887) 16 43,5 High intensity 45 statin mono (n=764) 22 Ezetimibe 54 combo 21 (n=189) 37,5 67 PCSK9i (n=24) 58 15 Other LLT 8 (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.

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 19