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Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels

      Abstract

      Patients with combined hyperlipidemia and low high-density lipoprotein (HDL) cholesterol levels may benefit from combination therapy with a statin and niacin; therefore, we assessed the efficacy and safety of rosuvastatin and extended-release (ER) niacin alone and in combination in 270 patients with this atherogenic dyslipidemia. Men and women ≥18 years with fasting total cholesterol levels ≥200 mg/dl, triglycerides 200 to 800 mg/dl, apolipoprotein B ≥110 mg/dl, and HDL cholesterol <45 mg/dl were randomized to 1 of 4 treatments in this 24-week, open-label, multicenter trial: rosuvastatin 10 to 40 mg; ER niacin 0.5 to 2 g; rosuvastatin 40 mg/ER niacin 0.5 to 1 g; or rosuvastatin 10 mg/ER niacin 0.5 to 2 g. Percent changes from baseline in low-density lipoprotein (LDL) cholesterol, non-HDL cholesterol, and other lipid measurements at week 24 were determined by analysis of variance, with statistical testing performed separately between the rosuvastatin monotherapy group and each remaining treatment group. Daily doses of rosuvastatin 40 mg reduced LDL and non-HDL cholesterol significantly more than either ER niacin 2 g or rosuvastatin 10 mg/ER niacin 2 g (−48% vs −0.1% and −36% for LDL cholesterol and −49% vs −11% and −38% for non-HDL cholesterol, respectively; p <0.01 for all comparisons); no additional reduction in LDL or non-HDL cholesterol was observed with the combination of rosuvastatin 40 mg/ER niacin 1.0 g (−42% and −47%; p = NS). Triglyceride reductions ranged from −21% (ER niacin monotherapy) to −39% (rosuvastatin 40 mg/ER niacin 1 g), but no observed differences were statistically significant. Compared with rosuvastatin alone, rosuvastatin 10 mg/ER niacin 2 g produced significantly greater increases in HDL cholesterol (11% vs 24%, p <0.001) and apolipoprotein A-I (5% vs 11%, p <0.017). Similar increases in HDL cholesterol and apolipoprotein A-I were noted between the monotherapy groups. Over 24 weeks, rosuvastatin alone was better tolerated than either ER niacin alone or the combinations of rosuvastatin and ER niacin.
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      References

        • Olsson A.G.
        • Pears J.
        • McKellar J.
        • Mizan J.
        • Raza A.
        Effects of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia.
        Am J Cardiol. 2001; 88: 504-508
        • Davidson M.H.
        • Ma P.T.S.
        • Stein E.
        • Gotto Jr, A.M.
        • Raza A.
        • Chitra R.
        • Hutchinson H.
        Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.
        Am J Cardiol. 2002; 89: 268-275
        • Paoletti R.
        • Fahmy M.
        • Mahla G.
        • Mizan J.
        • Southworth H.
        Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients.
        J Cardiovasc Risk. 2001; 8: 383-390
        • Olsson A.G.
        • Istad H.
        • Luurila O.
        • Ose L.
        • Stender S.
        • Tuomilehto J.
        • Wiklund O.
        • Southworth H.
        • Pears J.
        • Wilpshaar J.W.
        Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia.
        Am Heart J. 2002; 144: 1044-1051
        • Brown W.V.
        • Bays H.E.
        • Hassman D.R.
        • McKenney J.
        • Chitra R.
        • Hutchinson H.
        • Miller E.
        Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia.
        Am Heart J. 2002; 144: 1036-1043
        • Knopp R.H.
        • Ginsberg J.
        • Albers J.J.
        • Hoff C.
        • Ogilvie J.T.
        • Warnick G.R.
        • Burrows E.
        • Retzlaff B.
        • Poole M.
        Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects.
        Metabolism. 1985; 34: 642-650
        • Morgan J.M.
        • Capuzzi D.M.
        • Guyton J.R.
        • Centor R.M.
        • Goldberg R.
        • Robbins D.C.
        • DiPette D.
        • Jenkins S.
        • Marcovina S.
        Treatment effects of niaspan, a controlled-release niacin, in patients with hypercholesterolemia.
        J Cardiovasc Pharmacol Ther. 1996; 1: 195-202
        • Capuzzi D.M.
        • Guyton J.R.
        • Morgan J.M.
        • Goldberg A.C.
        • Kreisberg R.A.
        • Brusco O.A.
        • Brody J.
        Efficacy and safety of an extended-release niacin (niaspan).
        Am J Cardiol. 1998; 82: 74U-81U
        • Knopp R.H.
        • Alagona P.
        • Davidson M.
        • Goldberg A.C.
        • Kafonek S.D.
        • Kashyap M.
        • Sprecher D.
        • Superko H.R.
        • Jenkins S.
        • Marcovina S.
        Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.
        Metabolism. 1998; 47: 1097-1104
        • Goldberg A.
        • Alagona Jr, P.
        • Capuzzi D.M.
        • Guyton J.
        • Morgan J.M.
        • Rodgers J.
        • Sachson R.
        • Samuel P.
        Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia.
        Am J Cardiol. 2000; 85: 1100-1105
        • Peters J.R.
        • Quiter E.S.
        • Brekke M.L.
        • Admire J.
        • Brekke M.J.
        • Mullis R.M.
        • Hunninghake D.B.
        The eating pattern assessment tool.
        J Am Diet Assoc. 1994; 94: 1008-1013
        • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
        Summary of the Second Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II).
        JAMA. 1993; 269: 3015-3023
        • Myers G.L.
        • Cooper G.R.
        • Winn C.L.
        • Smith S.J.
        The Centers for Disease Control-National Heart, Lung, and Blood Institute lipid standardization program.
        Clin Lab Med. 1989; 9: 105-135
      1. Hainline A Jr, Karon J, Lippel K, eds. Lipid Research Clinics Program. Manual of Laboratory Operations: Lipid and Lipoprotein Analysis. 2nd Ed. Bethesda, MD: National Heart, Lung, and Blood Institute, NIH Publication 75–628 (revised), 1982

        • Steiner P.M.
        • Freidel J.
        • Bremmer W.F.
        • Stein E.A.
        Standardization of micromethods for plasma cholesterol, triglyceride and HDL-cholesterol with the Lipid Research Clinics’ methodology.
        J Clin Chem Clin Biochem. 1981; 19 (abstr): 850
        • Marcovina S.M.
        • Adolphson J.L.
        • Parlavecchia M.
        • Albers J.J.
        Effects of lyophilization of serum on the measurement of apolipoproteins A-I and B.
        Clin Chem. 1990; 36: 366-369
        • Marcovina S.M.
        • Albers J.J.
        • Henderson L.O.
        • Hannon W.H.
        International Federation of Clinical Chemistry standardization project for measurement of apolipoproteins A-I and B.
        Clin Chem. 1993; 39: 773-781
        • Vu Dac N.
        • Mezdour H.
        • Parra H.J.
        • Luc G.
        • Luyeye I.
        • Fruchart J.C.
        A selective bi-site immunoenzymatic procedure for human Lp(a) lipoprotein quantification using monoclonal antibodies against apo[a] and apoB.
        J Lipid Res. 1989; 30: 1437-1443
        • Montgomery D.C.
        Design, and Analysis of Experiments. 2nd Ed. John Wiley & Sons, New York, NY1984
        • Capuzzi D.M.
        • Morgan J.M.
        • Brusco O.A.
        • Intenzo C.M.
        Niacin dosing.
        Curr Atheroscler Rep. 2000; 2: 64-71
        • Knopp R.H.
        Evaluating niacin in its various forms.
        Am J Cardiol. 2000; 86: 51L-56L
        • Brown B.G.
        • Zhao X.-Q.
        • Chait A.
        • Fisher L.D.
        • Cheung M.C.
        • Morse J.S.
        • Dowdy A.A.
        • Marino E.K.
        • Bolson E.L.
        • Alaupovic P.
        • Frohlich J.
        • Albers J.J.
        Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease.
        N Engl J Med. 2001; 345: 1583-1592
        • Kashyap M.L.
        • McGovern M.E.
        • Berra K.
        • Guyton J.R.
        • Kwiterovich P.O.
        • Harper W.L.
        • Toth P.D.
        • Favrot L.K.
        • Kerzner B.
        • Nash S.D.
        • Bays H.E.
        • Simmons P.D.
        Long term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia.
        Am J Cardiol. 2002; 89: 672-678
        • Van J.T.
        • Pan J.
        • Wasty T.
        • Chan E.
        • Wu X.
        • Charles M.A.
        Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus.
        Am J Cardiol. 2002; 89: 1306-1308
        • Grundy S.M.
        • Vega G.L.
        • McGovern M.E.
        • Tulloch B.R.
        • Kendall D.M.
        • Fitz-Patrick D.
        • Ganda O.P.
        • Rosenson R.S.
        • Buse J.B.
        • Robertson D.D.
        • Sheehan J.P.
        Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes.
        Arch Intern Med. 2002; 162: 1568-1576
        • Guyton J.R.
        • Blazing M.A.
        • Hagar J.
        • Kashyap M.L.
        • Knopp R.H.
        • McKenney J.M.
        • Nash D.T.
        • Nash S.D.
        Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol.
        Arch Intern Med. 2000; 160: 1177-1184
        • Pan J.
        • Van J.T.
        • Chan E.
        • Kesala R.L.
        • Lin M.
        • Charles M.A.
        Extended-release niacin treatment of the atherogenic lipid profile and lipoprotein(a) in diabetes.
        Metabolism. 2002; 51: 1120-1127
        • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
        Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III).
        JAMA. 2001; 285: 2486-2497