prise en charge par cholesfytol & cholesfytol plus du...

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