MERCK NOVARTIS MEDTRONIC

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1 Τροφοφάρµακα (Nutraceuticals): Mια νέα εναλλακτική διαχείριση της δυσλιπιδιµίας στη συνδυασµένη θεραπευτική αγωγή...

2 MERCK NOVARTIS MEDTRONIC

3 Συχνότητα θανάτων από Καρδιαγγειακή Νόσο Άνδρες Γυναίκες (%) (%) στην Ευρώπη Άνδρες Γυναίκες (%) (%) Adapted from AHA Heart and Stroke Statistical Update.

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5 Atherothrombosis: a Generalized Normal and Progressive Process Fatty streak Fibrous plaque Atherosclerotic plaque Plaque rupture/ fissure & thrombosis Unstable angina MI }ACS Ischemic stroke/tia Clinically silent Stable angina Intermittent claudication Critical leg ischemia Cardiovascular death Increasing age ACS, acute coronary syndrome; TIA, transient ischemic attack

6 Αύξηση Κινδύνου Δευτεροπαθής πρόληψη Πρωτοπαθής πρόληψη 4S LIPID CARE WOSCOPS AFCAPS/TexCAPS.. X.. / X.. X.. X..

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9 EUROASPIRE II: Mόλις το 61% των ασθενών που χρειάζονται αγωγή παίρνουν υπολιπιδαιµική θεραπεία BEL/GHE CZE/PP FIN/KUO FRA/LLRT GER/MUNS GRE/ATCI HUN/BUD IRE/DUB ITA/TV NET/ROT POL/CRA SLO/LJU SPA/BAR SWE/MAL UK/HL ALL by center EUROASPIRE II. Eur Heart J 2001; 22: * total cholesterol < 5 mmol/l European Society of Cardiology ESC 76 79

10 BEL/GHE CZE/PP FIN/KUO FRA/LLRT GER/MUNS EUROASPIRE II: Mόλις το 51% των ασθενών σε υπολιπιδαιµική θεραπεία πέτυχε το στόχο GRE/ATCI HUN/BUD IRE/DUB ITA/TV NET/ROT POL/CRA SLO/LJU SPA/BAR SWE/MAL UK/HL ALL by center EUROASPIRE II. Eur Heart J 2001; 22: * total cholesterol < 5 mmol/l European Society of Cardiology ESC

11 69. Sirtori CR, Galli C, Anderson JW, Arnoldi A. Nutritional and nutraceutical approaches to dyslipidemia and atherosclerosis prevention: focus on dietary proteins. Atherosclerosis 2009;203: Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial. Ann Intern Med 2009;150: Lu Z, Kou W, Du B, Wu Y, Zhao S, Brusco OA, Morgan JM, Capuzzi DM, Li S;Chinese Coronary Secondary Prevention Study Group. Effect of Xuezhikang, anextract from red yeast Chinese rice, on coronary events in a Chinese populationwith previous myocardial infarction. Am J Cardiol 2008;101: Mas R, Castano G, Illinait J, Ferna ndez L, Ferna ndez J, Alema n C, Pontigas V, Lescay M. Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors. Clin Pharmacol Ther 1999;65: Reiner Z, Tedeschi-Reiner E, Romic Z. Effects of rice policosanol on serum lipoproteins, homocysteine, fibrinogen and C- reactive protein in hypercholesterolaemic patients. Clin Drug Investig 2005;25:

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13 (nutriceuticals) ;

14 . 1980

15 (FOSHU) [Foods for Specified Health Use],

16 , 1994 (DSHEA) [Dietary Supplement & Health Education Act],

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18 Selection of randomized placebo controlled studies for meta-analysis of plant sterols and circulating cholesterol levels

19 Effect size and 95% CI in LDL cholesterol levels associated with consumption of plant sterol/stanol containing food products.

20 Forest plots depicting the effect of plant sterols or stanols on (A) total cholesterol, (B) low-density lipoprotein cholesterol, (C) high-density lipoprotein cholesterol, and (D) triglycerides. All results reported as weighted mean differences (in mg/ dl) and 95% confidence intervals.

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23 Nutraceuticals /.. 100%...

24 Δραστικά Συστατικά ( ) Monascus purpureus Q10,

25 Κόκκινη Μαγιά (Mονακολίνη) 200 mg (3 mg) Πολυκοσανόλη 10 mg 1 = Φυλλικό Οξύ Συνένζυµο Q 10 Aσταξανθίνη 0,2 mg 2,0 mg 0,5 mg

26 Πολυκοσανόλη. HMGCoA r.. Castano G.et al.int.j.clin.pharm.res.2001;21:43-57

27 Comparison of the effects of policosanol and atorvastatin on lipid profile and platelet aggregation in patients with dyslipidaemia and type 2 diabetes mellitus. Castaño G, Fernández L, Mas R, Illnait J, Mesa M, Fernández JC. Medical Surgical Research Center, Havana City, Cuba. Policosanol (10 mg/day) for 8 weeks was less effective than similar doses of atorvastatin in reducing LDL-C and TC in patients with dyslipidaemia due to type 2 diabetes, but more effective in increasing HDL-C. Both drugs similarly reduced the TC/HDL-C ratio and triglycerides. Policosanol showed additional advantages regarding inhibition of platelet aggregation. Nevertheless, further studies of longer duration and using dose-titration schemes to achieve LDL-C goals are needed for wider conclusions about the respective effects of these two drugs in such a population subset. Clin Drug Investig. 2003;23(10):639-50

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31 DIABETES CARE, VOLUME 18, NUMBER 3, MARCH 1995

32 Am J Clin Nutr December 2006 vol. 84 nam J Clin Nutr December 2006 vol. 84 no o

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34 The impact of dietary changes and dietary supplements on lipid profile Systematic review / Meta-analysis Level of evidence Size of treatment effect Class I Class IIa Class IIb Class III Level A Multiple populations (3-5) evaluated Data derived from multiple RCTs or meta-analyses Level B Limited populations evaluated Data derived from single RCT or nonrandomized studies Level C Very limited population evaluated Only consensus opinion of experts, case studies, or standard of care Benefit >>> risk Little or no conflicting evidence Fully recommend Soy protein High fibre diet Phytostarols Whole grain food Low-fat diet Mediterranean diet Portfolio diet -3 fatty acids Might be useful Nuts Green tea Red wine High-CHO diet High-protein diet Benefit >> risk Some conflicting evidence; additional studies with focused objectives needed Reasonable to recommend Policosanol Red yeast rice extract Benefit risk More conflicting evidence; additional studies with broad objectives needed Probably not recommend Guggulipid Risk Benefit No additional studies needed Cannot recommend Garlic Might be useful Not recommend Not recommended Chromium MPPG Vitamin C Tocopherols Absorbitol Might be useful Nor recommended Not recommended Not recommended Huang J et al Can J Cardiol 2011;27:

35 PATIENTS A total of 4596 patients from 52 eligible studies.

36 CONCLUSION: Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy.

37 Μονακολίνη Monascus purpureus.. Δράση Ανταγωνίζεται στερεοχηµικά την HMGCoA r. Αναστέλλει την βιοσύνθεση της χοληστερόλης. Heber B,et al.am.j.cl.nutr.1999:69:

38 Υπολιπιδαιµική Δράση

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44 Improving the Diet Efficacy in Hypercholesterolemic Subjects with Red Yeast Rice Plus Policosanols. Achille P.Caputi, Claudio Benvenuti

45 Σκοπός Μελέτης Παράλληλη, τυχαιοποιηµένη, πολυκεντρική µελέτη (16 εβδοµάδων), όπου αξιολογήθηκε η αποτελεσµατικότητα και ασφάλεια του + δίαιτα (A+D) και της δίαιτας (D) µόνο, σε δυσλιπιδαιµικούς ασθενείς. Πληθυσµός ασθενείς (55+) 411 κέντρα ΤC>260, LDL>160, TG>170, HDL<50 Caputi, Benvenuti.L Internista Aprile 2008

46 Πληθυσµός Μελέτης Ασθενείς µε µη φυσιολογικά επίπεδα λιπιδίων Total Cholesterol LDL c >200 mg/dl >150 mg/dl Κριτήρια Αποκλεισµού Εγκυµοσύνη Θηλασµός Υπερτασική αγωγή Άλλη υπολιπιδαιµική θεραπεία Caputi, Benvenuti.L Internista Aprile 2008

47 Μείωση Ολικής Χοληστερόλης p<0, Διαφορά από έναρξη(%) ,9-13,4 8-7,2-15, , ,8 εβδοµάδες A+Δ n= Δ n= Caputi, Benvenuti.L Internista Aprile 2008

48 Μείωση LDL-c p<0,01 Διαφορά από έναρξη(%) ,4 4-4,6-13,8 8-6,7-15,7 12-7,1-18,6 16-9,1 εβδοµάδες A+Δ n= Δ n= Caputi, Benvenuti.L Internista Aprile 2008

49 Αύξηση HDL-c p<0, ,3 Διαφορά από έναρξη(%) ,2 2,8 7,9 8,6 2,7 4, εβδοµάδες A+Δ n= Δ n= Caputi, Benvenuti.L Internista Aprile 2008

50 Μείωση TR p<0,01 Διαφορά από έναρξη(%) εβδοµάδες A+Δ n= Δ n= Caputi, Benvenuti.L Internista Aprile 2008

51 Aνεπιθύµητες Ενέργειες Tύπος Μελέτης Ελεγχόµενη Ανοιχτή Θεραπεία (no ασθενών) Δίαιτα (n=1079) % A + Δ (n=1223) % Α + Δ (n=1325) % ΓΑΣΤΡΕΝΤΕΡΟΛΟΓΙΚΑ 0,37 1,23 0,60 ΝΕΥΡΟΛΟΓΙΚΑ 0,09 0,33 0,08 ΜΥΟΣΚΕΛΕΤΙΚΑ 0 0,25 0,38 ΔΕΡΜΑΤΙΚΑ 0 0 0,08 ΑΙΜΑΤΟΛΟΓΙΚΑ 0 0,08 0 ΣΥΝΟΛΟ 0,46 1,88 1,13 no. αποχωρήσεων οφειλόµενων στην θεραπεία(%)* 0, Caputi, Benvenuti.L Internista Aprile 2008

52 Συµπεράσµατα : / / Caputi, Benvenuti.L Internista Aprile 2008

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54 Σχεδιασµός Μελέτης : 1) N (EZE),. 2) ArmoLIPID+EZE,. 3) ArmoLIPID +. Pisciotta et al. Lipids in Health and Disease 2012, 11:123

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58 Συµπεράσµατα είναι αποτελεσµατικότερος και καλύτερα ανεκτός από την εζετιµίβη στην πολυγονιδιακή υπερχοληστερολαιµία. Μείωσε την ΤC:24% Mείωσε την LDL:32% Μείωσε τα TG:20% Το ΑrmoLIPID είναι µια αποτελεσµατική συµπληρωµατική θεραπεία στην ήδη υπάρχουσα αγωγή (στατίνη ή στατίνη +εζετιµίβη) στην οικογενή υπερχοληστερολαιµία, µε καλύτερα αποτελέσµατα έναντι του διπλασιασµού δόσης στατίνης. Pisciotta et al. Lipids in Health and Disease 2012, 11:123

59 Cicero, Benvenuti.Med.J.Nutr.& Metab.Oct 2010 he treatment of hypercholesterolemic children: Efficacy and safety of a combination of red yeast rice extract and policosanols.

60 Μελέτη,, PC, + (A+D) (D), : 8

61 Αποτελέσµατα Parameter Baseline Dietary Placebo Mean absolute P Supplement change (95% CI) TC mmol/l (-1.13 to -0.75) <0.001 LDLC, mmol/l (-1 to -0.68) <0.001 ApoB, g/l (-0.26 to -0.18) <0.001 HDLC, mmol/l (0.007 to 0.006) TG, mmol/l (-0.35 to -0.50) ApoA1, g/l ( to 0.1) nonhdlc, (-1.1 to -0.76) <0.001 mmol/l Guardamagna O et al Nutr Metab Cardiovasc Dis 2010

62 Συµπέρασµα. Cicero, Benvenuti.Med.J.Nutr.& Metab.Oct 2010

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64 Conclusion: Red yeast rice and therapeutic lifestyle change decrease LDL cholesterol level without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.

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