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Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease

Published:October 02, 2015DOI:https://doi.org/10.1016/j.amjcard.2015.09.023
      Statins are extensively used to treat dyslipidemia, but, because of their low tolerability profile, they are discontinued in a significant proportion of patients. Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated. A single-blind, single-center, randomized, prospective, and parallel group trial comparing a combination of nutraceuticals (red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin), called Armolipid Plus, and ezetimibe for 3 months in terms of efficacy and tolerability. Patients who did not achieve their therapeutic target (low-density lipoprotein cholesterol <100 mg/dl) could add the alternative treatment on top of randomized treatment for another 12 months: 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled (ezetimibe n = 50, nutraceutical n = 50). Efficacy (lipid profile) and tolerability (adverse events, transaminases, and creatine kinase) were assessed after 3 and 12 months. After 3 months, 14 patients in the nutraceutical group achieved their therapeutic target, whereas none of the patients in the ezetimibe group did. At 1-year follow-up, 58 patients (72.5%) of the combined therapy group (n = 86) and 14 (100%) of the nutraceutical group reached the therapeutic goal. No patients experienced important undesirable effects. In conclusion, nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease. Further studies are needed to assess long-term effects of nutraceuticals on mortality.
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      References

        • Kalra E.K.
        Nutraceutical-definition and introduction.
        AAPS Pharm Sci. 2003; 5: E25
        • Endo A.
        The origin of the statins. 2004.
        Atheroscler Suppl. 2004; 5: 125-130
        • Halbert S.C.
        • French B.
        • Gordon R.Y.
        • Farrar J.T.
        • Schmitz K.
        • Morris P.B.
        • Thompson P.D.
        • Rader D.J.
        • Becker D.J.
        Tolerability of red yeast rice (2,400 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance.
        Am J Cardiol. 2010; 105: 198-204
        • Karl M.
        • Rubenstein M.
        • Rudnick C.
        • Brejda J.
        A multicenter study of nutraceutical drinks for cholesterol (evaluating effectiveness and tolerability).
        J Clin Lipidol. 2012; 6: 150-158
        • Cicero A.F.
        • Derosa G.
        • Parini A.
        • Maffioli P.
        • D'Addato S.
        • Reggi A.
        • Giovannini M.
        • Borghi C.
        Red yeast rice improves lipid pattern, high-sensitivity C-reactive protein, and vascular remodeling parameters in moderately hypercholesterolemic Italian subjects.
        Nutr Res. 2013; 33: 622-628
        • Becker D.J.
        • Gordon R.Y.
        • Halbert S.C.
        • French B.
        • Morris P.B.
        • Rader D.J.
        Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial.
        Ann Intern Med. 2009; 150: 830-839
        • Bogsrud M.P.
        • Ose L.
        • Langslet G.
        • Ottestad I.
        • Strøm E.C.
        • Hagve T.A.
        • Retterstøl K.
        HypoCol (red yeast rice) lowers plasma cholesterol- a randomized placebo controlled study.
        Scand Cardiovasc J. 2010; 44: 197-200
        • Affuso F.
        • Mercurio V.
        • Fazio V.
        • Fazio S.
        Cardiovascular and metabolic effects of Berberine.
        World J Cardiol. 2010; 2: 71-77
        • Cicero A.F.
        • Rovati L.C.
        • Setnikar I.
        Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation.
        Arzneimittelforschung. 2007; 57: 26-30
        • Ruscica M.
        • Gomaraschi M.
        • Mombelli G.
        • Macchi C.
        • Bosisio R.
        • Pazzucconi F.
        • Pavanello C.
        • Calabresi L.
        • Arnoldi A.
        • Sirtori C.R.
        • Magni P.
        Nutraceutical approach to moderate cardiometabolic risk: results of a randomized, double-blind and crossover study with Armolipid Plus.
        J Clin Lipidol. 2014; 8: 61-68
        • Barrat E.
        • Zaïr Y.
        • Ogier N.
        • Housez B.
        • Vergara C.
        • Maudet C.
        • Lescuyer J.F.
        • Bard J.M.
        • Carpentier Y.A.
        • Cazaubiel M.
        • Peltier S.L.
        A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial.
        Int J Food Sci Nutr. 2013; 64: 882-889
        • Pisciotta L.
        • Bellocchio A.
        • Bertolini S.
        Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its addictive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment.
        Lipids Health Dis. 2012; 11: 123
        • Marazzi G.
        • Cacciotti L.
        • Pelliccia F.
        • Iaia L.
        • Volterrani M.
        • Caminiti G.
        • Sposato B.
        • Massaro R.
        • Grieco F.
        • Rosano G.
        Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients.
        Adv Ther. 2011; 28: 1105-1113
        • Levey A.S.
        • Coresh J.
        • Greene T.
        • Stevens L.A.
        • Zhang Y.L.
        • Hendriksen S.
        • Kusek J.W.
        • Van Lente F.
        • Chronic Kidney Disease Epidemiology Collaboration
        Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.
        Ann Intern Med. 2006; 45: 247-254
        • Endo A.
        Chemistry, biochemistry, and pharmacology of HMG-CoA reductase inhibitors.
        Klin Wochenschr. 1988; 66: 421-427
        • Man R.Y.
        • Lynn E.G.
        • Cheung F.
        • Tsang P.S.
        • O K
        Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2).
        Mol Cell Biochem. 2002; 233: 153-158
        • Menendez R.
        • Amor A.M.
        • Rodeiro I.
        • González R.M.
        • González P.C.
        • Alfonso J.L.
        • Más R.
        Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts.
        Arch Med Res. 2001; 32: 8-12
        • Cameron J.
        • Ranheim T.
        • Kulseth M.A.
        • Leren T.P.
        • Berge K.E.
        Berberine decreases PCSK9 expression in HepG2 cells.
        Atherosclerosis. 2008; 201: 266-273
        • Kong W.
        • Wei J.
        • Abidi P.
        • Lin M.
        • Inaba S.
        • Li C.
        • Wang Y.
        • Wang Z.
        • Si S.
        • Pan H.
        • Wang S.
        • Wu J.
        • Wang Y.
        • Li Z.
        • Liu J.
        • Jiang J.D.
        Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.
        Nat Med. 2004; 10: 1344-1351
        • Pandor A.
        • Ara R.M.
        • Tumur I.
        • Wilkinson A.J.
        • Paisley S.
        • Duenas A.
        • Durrington P.N.
        • Chilcott J.
        Ezetimibe monotherapy for cholesterol lowering in 2722 people: systematic review and meta-analysis of randomized controlled trials.
        J Intern Med. 2009; 265: 568-580
        • Affuso F.
        • Ruvolo A.
        • Micillo F.
        • Saccà L.
        • Fazio S.
        Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study.
        Nutr Metab Cardiovasc Dis. 2010; 20: 656-661
        • Cicero A.F.
        • Ferroni A.
        • Ertek S.
        Tolerability and safety of commonly used dietary supplements and nutraceuticals with lipid-lowering effects.
        Expert Opin Drug Saf. 2012; 11: 753-766
        • Affuso F.
        • Mercurio V.
        • Ruvolo A.
        • Pirozzi C.
        • Micillo F.
        • Carlomagno G.
        • Grieco F.
        • Fazio S.
        A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome.
        World J Cardiol. 2012; 4: 77-83
        • Solà R.
        • Valls R.M.
        • Puzo J.
        • Calabuig J.R.
        • Brea A.
        • Pedret A.
        • Moriña D.
        • Villar J.
        • Millán J.
        • Anguera A.
        Effects of poly-bioactive compounds on lipid profile and body weight in a moderately hypercholesterolemic population with low cardiovascular disease risk: a multicenter randomized trial.
        PLoS One. 2014; 9: e101978
        • Banach M.
        • Rizzo M.
        • Toth P.P.
        • Farnier M.
        • Davidson M.H.
        • Al-Rasadi K.
        • Aronow W.S.
        • Athyros V.
        • Djuric D.M.
        • Ezhov M.V.
        • Greenfield R.S.
        • Hovingh G.K.
        • Kostner K.
        • Serban C.
        • Lighezan D.
        • Fras Z.
        • Moriarty P.M.
        • Muntner P.
        • Goudev A.
        • Ceska R.
        • Nicholls S.J.
        • Broncel M.
        • Nikolic D.
        • Pella D.
        • Puri R.
        • Rysz J.
        • Wong N.D.
        • Bajnok L.
        • Jones S.R.
        • Ray K.K.
        • Mikhailidis D.P.
        Statin intolerance- an attempt at a unified definition. Position paper from an International Lipid Expert Panel.
        Arch Med Sci. 2015; 11: 1-23