Lipid Management in 2020: A Glimpse into the Future - Prof Kausik Ray FESC, FACC, FAHA
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Lipid Management in 2020:
A Glimpse into the Future
Prof Kausik Ray
MBChB, MD, MPhil (Cantab), FRCP (Lon), FRCP (Ed),
FESC, FACC, FAHA
School of Public Health,
Imperial College London, London, UK
CVD will still be a problem in 2020!
Why ?
• Public Health • Therapies
• Lifestyle • Inadequate use of
• Increased life evidence based
expectancy treatments
• Awareness/ Knowledge • Side effects of current
• Treating more advanced Tx
disease • Treatment threshold
• Lack of Screening has been reached
• Cost
CEPHEUS: about half of patients
achieved LDL-C goals
Patients on lipid-lowering drugs for >3 months
(stable medication >6 weeks)
90
83
Europe1 Asia2
80 JETF guidelines NCEP ATP III guidelines*
% of patients at LDL-C goal
70 68
65
59 61
60
51 53
49 48 49 50
50 45
41 40 40
40
31
30
20
10
0
*Patients with ≥2 cardiovascular risk factors according to NCEP ATP III guidelines;
CEPHEUS, CEntralized Pan-European survey on tHE Under-treatment of hypercholeSterolaemia,
NCEP ATP, National Cholesterol Educational Program Adult Treatment Panel; JETF, Joint European Task Force
1. Hermans MP et al. Curr Med Res Opin 2010;26:445–454;
2. Park JE et al. Eur J Prev Cardiol 2012;19:781–794
What will change? • Revolution in the management of FH • Screening and Earlier Treatment to Prevent CVD • More widespread understanding and use of absolute risk scores to
Familial Hypercholesterolaemia Estimated millions of individuals worldwide with FH by WHO regions and by income groups Nordestgaard BG et al. Eur Heart J 2013;34:3478-3490
Familial Hypercholesterolaemia
Estimated % of
individuals diagnosed
with FH in different
countries/ territories,
as a fraction of those
theoretically predicted
based on a frequency
of 1/500 in the
general population
Nordestgaard BG et al. Eur Heart J 2013;34:3478-3490Despite available treatment approaches, we still have a
significant percentage of patients not at goal
100
Attainment of target (%)
80
60
40
20
0
0 2 3 4 5 6 7 8 9 10
LDL-C target (mmol/l)
• Pijlman AH et al. Atherosclerosis 2009;209:189–194Familial Hypercholesterolaemia
LDL-C burden in individuals with or without FH as a function of the age of initiation of statin therapy
Nordestgaard BG et al. Eur Heart J 2013;34:3478-3490Solutions • Awareness/ Improve Knowledge • Screening systematically • Change Policy/ ICD codes • Additional new therapies
www.eas-society.org
RUTHERFORD-2: LDL-Ca goal achievement
400 mg/dL; bpMost heFH Patients Receiving Alirocumab on
Background Statin Other LLT Achieved LDL-C Goals
Proportion of patients reaching LDL-C goal† at Week 24
90
FH I 81.4% FH II
80 Alirocumab
72.2%
70
Placebo
60
% patients
50
40
30 PPreserve Health vs Treating Disease
Screen early, treat early,
think about lifetime risk
54.5% relative risk reduction 22% relative risk reduction
per 1 mM/L (38.7mg/dL) per 1 mmol/L (38.7mg/dL)
LDL-C lowering LDL-C lowering
Major vascular events
50%
30%
40%
Proportional reduction in event rate (SE)
Proportional Risk Reduction (SE)
rs11591147
30%
20%
rs4420638
20%
rs646776 rs6511720
rs2228671 rs599839
10%
rs12916 10%
rs11206510
rs4299376
0%
0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.013.0 14.015.0 16.0 17.0 18.0
0.5 1.0 1.5 2.0
Lower LDL-C (mg/dL)
-10%
Reduction in LDL cholesterol (mmol/L)
Ference BA et al. J Am Coll Cardiol 2012;60:2631–2639; Baigent C et al. Lancet 2005;366:1267–1278Solutions • Systematic Screening • Exemplar NHS Vascular Health Checks being offered in the UK to everyone aged 40-70
Problems • Visualising absolute risk in a n individual is poor • Reluctance to use higher doses based on unfounded concerns • Wait and watch approach
The Need for Absolute Risk
Prediction for People on Statin
TherapyRelationship of LDL-C lowering and Risk Reduction with a statin
~ 20% reduction in RR per mmol LDL-C
Consistent effect on relative risk; diminishing effect on absolute risk
8% As abs risk
-20% = 1.6% abs RR
Log of Risk
-20% = 1.3% abs RR
NNT
-20% = 1% abs RR
-20% = 0.8% abs RR
3.3%
0 1 2 3 4 5 6
LDL-C mmoles• Bhatt JAMA REACH REGISTRY
• Bhatt JAMA REACH REGISTRYc
Other Therapies
CETP Inhibition HDL pathways Anti Inflammatory Other
Tx
Anacetrapib Apo A mimetics IL-1B inhibtion Target Lp(a)
Evacetrapib A1 Milano Methotrexate Target Apo C III
TA 8995 RVX 208 PPAR alpha agonists
High Dose fish oilsOverall rates of secondary prevention medication
use for CVD is low worldwide
PURE study, 17 countries
100
Antiplatelet Beta-blockers ACEi or ARBs Diuretics BP-lowering Ca-channel blockers Statin
% of patients with treatment
80
60
43 42
40
40
26 24 25
20 20 19 20
17 15 17
20 14 13 14 14 13 15
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;378:1231–1243Conclusion • All these emerging therapies will increase uptake of statins and other current Tx • FH will be better detected (hope), better treated yes • Screen and treat early • Need to be more sophisticated about who we offer additional Tx to
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