Prise en charge par Cholesfytol & Cholesfytol Plus du patient hypercholestérolémique 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
Is Lower Better? Relationship between LDL- C and CV Event Rate 30 4S - Pl Event rate (%) 25 20 15 10 5 0 40 (1.0) Rx - Statin therapy Pl Placebo Pra pravastatin Atv - atorvastatin LIPID - Rx AFCAPS - Rx ASCOT - Rx 4S - Rx CARE - Rx HPS - Rx TNT Atv10 TNT Atv80 PROVE-IT - Pra PROVE-IT Atv 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) HPS - Pl AFCAPS - Pl ASCOT - Pl LDL-C achieved mg/dl (mmol/l) Secondary Prevention CARE - Pl 140 (3.6) LIPID - Pl WOSCOPS Pl WOSCOPS - Rx 160 (4.1) 180 (4.7) Rosenson RS. Exp Opin Emerg Drugs 2004;9(2):269-279, LaRosa JC et al. N Engl J Med 2005;352:1425-1435. 6 Primary Prevention 200 (5.2)
Relationship Between Proportional Reduction in Events and Mean LDL-C Reduction at 1 Year Proportional reduction in event rate (%±SE) 50 40 30 20 10 0-10 Major coronary events 0.5 (19) 1.0 (38) 1.5 (58) 2.0 (77) Proportional reduction in event rate (%±SE) 50 40 30 20 10 0-10 Major vascular events 0.5 (19) 1.0 (38) 1.5 (58) 2.0 (77) Reduction in LDL-C mmol/l (mg/dl) Reduction in LDL-C mmol/l (mg/dl) CTT Collaborators. Lancet 2005;366:1267 1278.
Lipids & lipoproteins l LDL-C hypercholesterolemia l HDL-C l non-hdl-c l apolipoprotein B 100 (apob) atherogenic dyslipidemia 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)
Nutritional-physical activity imbalance Proinflammatory state muscle insulin resistance genetic &/or acquired mitochondrial defects (density/function/biogenesis) oxidation capacity: sarcopenia, fiber type & distribution, ageing, obesity adipocyte dysregulation IR-inducing secretory products and NEFAs; adiponectin Atherogenic dyslipidemia apob-vldl-tg lipoproteins glucose output hepatic insulin resistance hepatic lipogenesis NAFL, NAFLD, NASH chronic hyperinsulinaemia IFG-IGT / T2DM in predisposed individuals
muscle insulin resistance Nutritional-physical activity imbalance Proinflammatory state $ genetic &/or acquired mitochondrial defects (density/function/biogenesis) oxidation capacity: sarcopenia, fiber type & distribution, ageing, obesity! adipocyte dysregulation IR-inducing secretory products and NEFAs; adiponectin Atherogenic dyslipidemia " # apob-vldl-tg lipoproteins glucose output hepatic insulin resistance % hepatic lipogenesis NAFL, NAFLD, NASH chronic hyperinsulinaemia IFG-IGT / T2DM in predisposed individuals
(epi) genetic factors environmental cardiometabolic RFs standard RFs Beta-cell failure overweight - obesity metabolic syndrome age gender gestational diabetes IR / hyperinsulinemia hypertension pre-diabetes chronic kidney disease smoking T2DM atherogenic dyslipidemia LDL-C chronic hyperglycemia (surrogate: HbA1c) microvascular disease (DRP - PNP - DN) macrovascular disease (CAD - PAD - CVD)
Cholesfytol Levure rouge de riz (LRR): monacoline K 10 mg ( 80% forme OHacide) Extrait d olives: hydroxytyrosol 5 mg Cholesfytol Plus Levure rouge de riz (LRR): monacoline K 10 mg ( 80% forme OH-acide) Extrait d olives: hydroxytyrosol 10 mg
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 ++
Efficacité thérapeutique 81 jours
Efficacité thérapeutique 81 jours 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 30 4S - Pl Event rate (%) 25 20 15 10 5 0 40 (1.0) Rx - Statin therapy Pl Placebo Pra pravastatin Atv - atorvastatin LIPID - Rx AFCAPS - Rx ASCOT - Rx 4S - Rx CARE - Rx HPS - Rx TNT Atv10 TNT Atv80 PROVE-IT - Pra PROVE-IT Atv 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) HPS - Pl AFCAPS - Pl ASCOT - Pl LDL-C achieved mg/dl (mmol/l) Secondary Prevention CARE - Pl 140 (3.6) LIPID - Pl WOSCOPS Pl WOSCOPS - Rx 160 (4.1) 180 (4.7) Rosenson RS. Exp Opin Emerg Drugs 2004;9(2):269-279, LaRosa JC et al. N Engl J Med 2005;352:1425-1435. 6 Primary Prevention 200 (5.2)
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