prise en charge par cholesfytol & cholesfytol plus du...
TRANSCRIPT
21 mai 2016 – LCB
Michel P. HERMANS
MD (UCL) PhD (UCL & Oxford, UK) Dip. Natural Sciences (Open University, Milton Keynes, UK) Dip. Earth Sciences (Open University, Milton Keynes, UK)
Dip. Human Geography (Open University, Milton Keynes, UK) Dip. Environment (Open University, Milton Keynes, UK)
PG CerNficate in Social Sciences (Open University, Milton Keynes, UK)
Endocrinologie & NutriNon Cliniques universitaires St-‐Luc
Université Catholique de Louvain
Prise en charge par Cholesfytol® & Cholesfytol Plus®
du patient hypercholestérolémique
Is Lower Better? Relationship between LDL-C and CV Event Rate
Rosenson RS. Exp Opin Emerg Drugs 2004;9(2):269-279, LaRosa JC et al. N Engl J Med 2005;352:1425-1435.
LDL-C achieved mg/dL (mmol/L)
WOSCOPS – Pl AFCAPS - Pl
ASCOT - Pl AFCAPS - Rx WOSCOPS - Rx
ASCOT - Rx
4S - Rx
HPS - Pl LIPID - Rx
4S - Pl
CARE - Rx
LIPID - Pl CARE - Pl
HPS - Rx
0
5
10
15
20
25
30
40 (1.0) 60
(1.6) 80 (2.1) 100
(2.6) 120 (3.1) 140
(3.6) 160 (4.1) 180
(4.7)
Even
t ra
te (
%)
6
Secondary Prevention
Primary Prevention
Rx - Statin therapy Pl – Placebo Pra – pravastatin Atv - atorvastatin
200 (5.2)
PROVE-IT - Pra PROVE-IT – Atv
TNT – Atv10 TNT – Atv80
Major coronary events
50
40
30
20
10
0 0.5 (19)
1.0 (38)
1.5 (58)
2.0 (77)
-10
Major vascular events
Reduction in LDL-C mmol/L (mg/dL)
50
40
30
20
10
-10
0
0.5 (19)
1.0 (38)
1.5 (58)
2.0 (77)
Reduction in LDL-C mmol/L (mg/dL)
Pro
por
tion
al r
edu
ctio
n in
eve
nt
rate
(%
±SE)
Pro
por
tion
al r
edu
ctio
n in
eve
nt
rate
(%
±SE)
CTT Collaborators. Lancet 2005;366:1267–1278.
Relationship Between Proportional Reduction in Events and Mean LDL-C Reduction at 1 Year
l LDL-C l HDL-C l non-HDL-C l apolipoprotein B100 (apoB)
– total burden of VLDL, IDL, LDL & Lp(a) l apolipoprotein A-I (apoA-I) : surrogate for HDL l TG-rich lipoproteins
– fasting TG : surrogate for VLDL – postprandial TG: combined VLDL, IDL, chylomycrons
l LDL number / size l Lipoprotein(a)
atherogenic dyslipidemia
hypercholesterolemia
Lipids & lipoproteins
muscle insulin resistance
genetic &/or acquired mitochondrial defects (density/function/biogenesis)
↓ oxidation capacity: sarcopenia, fiber type & distribution, ageing, obesity
Atherogenic dyslipidemia
hepatic insulin resistance
↑ apoB-VLDL-TG lipoproteins
IFG-IGT / T2DM in predisposed individuals
hepatic lipogenesis
NAFL, NAFLD, NASH
Proinflammatory state
↑ IR-inducing secretory products and NEFAs; ↓ adiponectin
↑ glucose output
chronic hyperinsulinaemia
Nutritional-physical activity imbalance
adipocyte dysregulation
muscle insulin resistance
genetic &/or acquired mitochondrial defects (density/function/biogenesis)
↓ oxidation capacity: sarcopenia, fiber type & distribution, ageing, obesity
Atherogenic dyslipidemia
hepatic insulin resistance
↑ apoB-VLDL-TG lipoproteins
IFG-IGT / T2DM in predisposed individuals
hepatic lipogenesis
NAFL, NAFLD, NASH
Proinflammatory state
↑ IR-inducing secretory products and NEFAs; ↓ adiponectin
↑ glucose output
chronic hyperinsulinaemia
Nutritional-physical activity imbalance
adipocyte dysregulation
! " #
$
%
(epi) genetic factors environmental cardiometabolic RFs standard RFs
overweight - obesity age
metabolic syndrome gender
gestational diabetes IR / hyperinsulinemia hypertension
pre-diabetes chronic kidney disease smoking
T2DM atherogenic dyslipidemia LDL-C
macrovascular disease (CAD - PAD - CVD)
chronic hyperglycemia (surrogate: HbA1c)
Beta-cell failure
microvascular disease (DRP - PNP - DN)
Levure rouge de riz (LRR): monacoline K 10 mg (≥80% forme OH-acide)
Extrait d’olives: hydroxytyrosol 5 mg
Levure rouge de riz (LRR): monacoline K 10 mg (≥80% forme OH-acide)
Extrait d’olives: hydroxytyrosol 10 mg
Cholesfytol
Cholesfytol Plus
monacoline K • riz fermenté par Monascus purpureus • Inhibiteur de l’HMG-CoA-réductase
• monacoline K – mévinoline – lovastatine (Aspergillus terreus)
Hydroxytyrosol • extra-vergin olive oil (EVOO) is a crucial component of Mediterranean diet • EVOO contains 30 phenolic compounds eg. oleuropein derivatives
• hydroxytyrosol : major phenolic component of EVOO (fruit and leaves of Olea europaea L)
• anti-oxidant (including LDL oxidation) • anti-endothelial dysfunction • inhibition of platelet activation • anti inflammatory
• European Food Safety Authority: 5 mg/day of hydroxytyrosol and its derivatives (LDL oxidation)
But et schéma de l’étude
• Objectif primaire: – efficacité thérapeutique – Cholesfytol® (1 co/jour le soir) – patients en hypercholestérolémie – étude observationnelle – prospective – non randomisée – médecins généralistes (MG)
Critères d’inclusion / exclusion • patients sans traitement (ou ayant arrêté le traitement 1 mois
avant le début de l’étude) • aucun autre traitement du cholestérol • CT : ≥ 200 mg/dl • LDL-C : ≥ 140 mg/dl • âge ≥ 21 ans
– historique de myalgie autorisé – diabétiques autorisés – femmes enceintes ou allaitantes exclues
Patients & Observance
• 126 MG • 642 patients • Observance ++
81 jours
Efficacité thérapeutique
81 jours
Efficacité thérapeutique
TG (mg/dL) 158 126 -‐20.3%
apoB100 (mg/dL) 136 106 -‐22.4%
LDL-‐C / apoB100 1.23 1.21 -‐2%
Efficacité thérapeutique: dyslipidémie athérogène à l’inclusion (21%)
TG (mg/dL) 235 181 -‐15%
HDL-‐C (mg/dL) 39.9 43.8 +10%
Lower is Better - Relationship between LDL-C and CV Event Rate
Rosenson RS. Exp Opin Emerg Drugs 2004;9(2):269-279, LaRosa JC et al. N Engl J Med 2005;352:1425-1435.
LDL-C achieved mg/dL (mmol/L)
WOSCOPS – Pl AFCAPS - Pl
ASCOT - Pl AFCAPS - Rx WOSCOPS - Rx
ASCOT - Rx
4S - Rx
HPS - Pl LIPID - Rx
4S - Pl
CARE - Rx
LIPID - Pl CARE - Pl
HPS - Rx
0
5
10
15
20
25
30
40 (1.0) 60
(1.6) 80 (2.1) 100
(2.6) 120 (3.1) 140
(3.6) 160 (4.1) 180
(4.7)
Even
t ra
te (
%)
6
Secondary Prevention
Primary Prevention
Rx - Statin therapy Pl – Placebo Pra – pravastatin Atv - atorvastatin
200 (5.2)
PROVE-IT - Pra PROVE-IT – Atv
TNT – Atv10 TNT – Atv80
Sous-groupes • Patients avec variables cardiométaboliques élevées à l’inclusion
Antécédent de myalgies sous LLD : 32%
Antécédent de myalgies sous LLD
Antécédent de myalgies sous LLD
Effets secondaires et poursuite du traitement
Inclusion: 32% avec antécédent de myalgies sous LLD
Conclusions
• monacoline K + hydroxytyrosol • efficacité thérapeutique hypercholestérolémie en MG
• -23% LDL-C – amélioration autres paramètres (dont lipides / lipoprotéines):
• TG – apolipoprotéine B100 (estimée) – non-HDL-C – CRP • TG et HDL chez sous-groupe avec dyslipidémie athérogène
• tolérance & persistance • patients avec historique de myalgies sous statines • neutralité homéostasie glucidique
• limitations • cfr design de l’étude