Combination treatment with atorvastatin plus niacin provides effective control of complex dyslipidemias: A literature review

Postgraduate Medicine

Volumn 124, Issue 1, 2012, Pages 7-20

  McKenney, James M ^a  

^a National Clinical Research Inc   (United States)

Author keywords

Atorvastatin; Dyslipidemia; High density lipoprotein; Niacin; Triglycerides

Indexed keywords

ACETYLSALICYLIC ACID; AMINOTRANSFERASE; ANTILIPEMIC AGENT; ANTIOXIDANT; ATORVASTATIN; COLESEVELAM; EZETIMIBE; FENOFIBRIC ACID; FIBRIC ACID DERIVATIVE; HEMOGLOBIN A1C; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NICOTINIC ACID; OMEGA 3 FATTY ACID; PLACEBO; PROSTAGLANDIN DERIVATIVE; ROSUVASTATIN; SIMVASTATIN; TRIACYLGLYCEROL; URIC ACID;

ARTERIAL WALL THICKNESS; ARTICLE; CARDIOVASCULAR RISK; CAROTID ARTERY; CHOLESTEROL BLOOD LEVEL; DIABETES MELLITUS; DISEASE CONTROL; DRUG EFFICACY; DRUG ERUPTION; DRUG FORMULATION; DRUG MEGADOSE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSLIPIDEMIA; FLUSHING; GASTROINTESTINAL SYMPTOM; GLYCEMIC CONTROL; HUMAN; HYPERTRANSAMINASEMIA; INSULIN SENSITIVITY; ISCHEMIC HEART DISEASE; LIVER TOXICITY; LOW DRUG DOSE; MONOTHERAPY; MYALGIA; MYOPATHY; PATIENT COMPLIANCE; PATIENT COUNSELING; PEPTIC ULCER; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PRIMARY PREVENTION; RISK REDUCTION; SECONDARY PREVENTION; SIDE EFFECT; TREATMENT RESPONSE; TRIACYLGLYCEROL BLOOD LEVEL;

CORONARY DISEASE; DRUG THERAPY, COMBINATION; DYSLIPIDEMIAS; FLUSHING; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPOLIPIDEMIC AGENTS; MEDICATION ADHERENCE; NIACIN; PYRROLES;

EID: 84856942270     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.3810/pgm.2012.01.2513     Document Type: Article

References (87)

1. 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) final report. Circulation. 2002;106(25):3143-3421.
2. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81(5):582-587.
3. Weng TC, Yang Y, Lin SJ, Tai SH. A systematic review and metaanalysis on the therapeutic equivalence of statins. J Clin Pharm Thera. 2010;35(2):139-151.
4. Dieleman JP, van Wyk JT, van Wijk MA, et al. Differences between statins on clinical endpoints: a population-based cohort study. Curr Med Res Opin. 2005;21(9):1461-1468.
5. Gresser U, Gathof BS. Atorvastatin: gold standard for prophylaxis of myocardial ischemia and stroke-comparison of the clinical benefit of statins on the basis of randomized controlled endpoint studies. Eur J Med Res. 2004;9(1):1-17.
6. Miller M. Differentiating the effects of raising low levels of highdensity lipoprotein cholesterol versus lowering normal triglycerides: further insights from the Veterans Affairs High-Density Lipoprotein Intervention Trial. Am J Cardiol. 2000;86(12A):23L-27L.
7. Bestehorn K, Smolka W, Pittrow D, Schulte H, Assmann G. Atherogenic dyslipidemia as evidenced by the lipid triad: prevalence and associated risk in statin-treated patients in ambulatory care. Curr Med Res Opin. 2010;26(12):2833-2839.
8. Abdel-Maksoud M, Sazonov V, Gutkin SW, Hokanson JE. Effects of modifying triglycerides and triglyceride-rich lipoproteins on cardiovascular outcomes. J Cardiovasc Pharmacol. 2008;51(4):331-351.
9. Musunuru K. Atherogenic dyslipidemia: cardiovascular risk and dietary intervention. Lipids. 2010;45(10):907-914.
10. Maruyama T, Takada M, Nishibori Y, et al. Comparison of preventive effect on cardiovascular events with different statins. Circ J. 2011;75(8): 1951-1959.
11. American Diabetes Association. Standards of medical care in diabetes-2008. Diabetes Care. 2008;31(suppl 1):S12-S54.
12. Pedersen TR, Assmann G, Bassand JP, Chapman MJ, Erbel R, Sirtori C. Reducing residual cardiovascular risk: the relevance of raising highdensity lipoprotein cholesterol in patients on cholesterol-lowering treatment. Diabetes Vasc Dis Res. 2006;3(suppl 2):S1-S12.
13. Chapman MJ, Redfern JS, McGovern ME, Giral P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010;126(3):314-345.
14. Isley WL, Miles JM, Harris WS. Pilot study of combined therapy with omega-3 fatty acids and niacin in atherogenic dyslipidemia. J Clin Lipidol. 2007;1(3):211-217.
15. Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: a meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2005;45(2):185-197.
16. Lovaza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2010.
17. Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412-423.
18. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331-2339.
19. Morgan JM, Carey CM, Lincoff A, Capuzzi DM. The effects of niacin on lipoprotein subclass distribution. Prev Cardiol. 2004; 7(4):182-187; quiz 188.
20. McKenney JM, McCormick LS, Schaefer EJ, Black DM, Watkins ML. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Am J Cardiol. 2001;88(3): 270-274.
21. Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Statin-fibrate combination for mixed dyslipidaemia: a limited option. Curr Med Res Opin. 2010;26(9):2137-2140.
22. Brown BG, Stukovsky KH, Zhao XQ. Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and their combinations: a meta-analysis of 23 randomized lipid trials. Curr Opin Lipidol. 2006;17(6):631-636.
23. Jones PH, Davidson MH, Goldberg AC, et al. Efficacy and safety of fenofibric acid in combination with a statin in patients with mixed dyslipidemia: Pooled analysis of three phase 3, 12-week randomized, controlled studies. J Clin Lipidol. 2009;3(2):125-137.
24. Franssen R, Vergeer M, Stroes ES, Kastelein JJ. Combination statin-fibrate therapy: safety aspects. Diabetes Obes Metab. 2009;11(2):89-94.
25. ACCORD Study Group; Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563-1574.
26. Tenenbaum A, Fisman EZ. "If it ain't broke, don't fix it": a commentary on the positive-negative results of the ACCORD Lipid study. Cardiovasc Diabetol. 2010;9:24.
27. US Food and Drug Administration. Summary minutes of the Endocrinologic and Metabolic Drugs Advisory Committee, May 9, 2011. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisory-Committee/UCM261162.pdf. Accessed October 27, 2011.
28. Nordoy A, Bonaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC. Effects of simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J Intern Med. 1998;243(2):163-170.
29. Durrington PN, Bhatnagar D, Mackness MI, et al. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85(5): 544-548.
30. Chan DC, Watts GF, Mori TA, Barrett PH, Beilin LJ, Redgrave TG. Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Eur J Clin Invest. 2002;32(6):429-436.
31. Davidson MH, Stein EA, Bays HE, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29(7):1354-1367.
32. Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/ day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Am J Cardiol. 2008;102(4):429-433.
33. Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010;85(2):122-128.
34. Kim SH, Kim MK, Lee HY, Kang HJ, Kim YJ, Kim HS. Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability. Eur J Clin Nutr. 2011;65(1):110-116.
35. Yokoyama M, Origasa H, Matsuzaki M, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-1098.
36. Wolfe ML, Vartanian SF, Ross JL, et al. Safety and effectiveness of niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol. 2001;87(4):476-479, A7.
37. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110(23): 3512-3517.
38. Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin. 2006;22(11):2243-2250.
39. Lee JM, Robson MD, Yu LM, et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol. 2009;54(19):1787-1794.
40. Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361(22):2113-2122.
41. Villines TC, Stanek EJ, Devine PJ, et al. The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol. 2010;55(24): 2721-2726.
42. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345(22):1583-1592.
43. Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210(2):353-361.
44. AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/ high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J. 2011;161(3):471-477.e42.
45. AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: impact on Global Health outcomes (AIMHIGH) trial. Am Heart J. 2011;161(3):538-543.
46. US National Institutes of Health. NIH stops clinical trial on combination cholesterol treatment [press release]. http://www.nih.gov/news/health/ may2011/nhlbi-26.htm. Accessed October 27, 2011.
47. AIM-HIGH Investigators; Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.
48. University of Oxford. Welcome to the THRIVE study. http://www. thrivestudy.org/index.htm. Accessed October 27, 2011.
49. US National Institutes of Health. Treatment of HDL to reduce the incidence of vascular events: HPS2-THRIVE. http://clinicaltrials.gov/ct/show/NCT00461630?order=1. Accessed October 27, 2011.
50. Tenenbaum A, Fisman EZ, Motro M, Adler Y. Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. Cardiovasc Diabetol. 2006;5:20.
51. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA. 1994;271(9):672-677.
52. Backes JM, Padley RJ, Moriarty PM. Important considerations for treatment with dietary supplement versus prescription niacin products. Postgrad Med. 2011;123(2):70-83.
53. Choi BG, Vilahur G, Yadegar D, Viles-Gonzalez JF, Badimon JJ. The role of high-density lipoprotein cholesterol in the prevention and possible treatment of cardiovascular diseases. Curr Mol Med. 2006;6(5):571-587.
54. Berge KG, Canner PL. Coronary drug project: experience with niacin. Coronary Drug Project Research Group. Eur J Clin Pharmacol. 1991;40(suppl 1):S49-S51.
55. McCormack PL, Keating GM. Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. Drugs. 2005;65(18):2719-2740.
56. Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B-26B.
57. Sanyal S, Kuvin JT, Karas RH. Niacin and laropiprant. Drugs Today (Barc). 2010;46(6):371-378.
58. Parhofer KG. Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia. Vasc Health Risk Manag. 2009;5:901-908.
59. Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in noninsulin- dependent diabetes mellitus. JAMA. 1990;264(6):723-726.
60. Molnar GD, Berge KG, Rosevear JW, McGuckin WF, Achor RW. The effect of nicotinic acid in diabetes mellitus. Metabolism. 1964;13: 181-190.
61. Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. Arterial Disease Multiple Intervention Trial. JAMA. 2000;284(10): 1263-1270.
62. Vega GL, Cater NB, Meguro S, Grundy SM. Influence of extendedrelease nicotinic acid on nonesterified fatty acid flux in the metabolic syndrome with atherogenic dyslipidemia. Am J Cardiol. 2005;95(11):1309-1313.
63. McKenney JM, Bays H, Koren M, et al. Safety of extended-release niacin/laropiprant in patients with dyslipidemia. J Clin Lipidol. 2010;4(2):105-112.e1.
64. Grundy SM, Vega GL, McGovern ME, et al; Diabetes Multlicenter Research Group. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med. 2002;162(14):1568-1576.
65. Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008;83(4):470-478.
66. Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. 2007; 99(6A):22C-31C.
67. Ginsberg HN. Niacin in the metabolic syndrome: more risk than benefit? Nat Clin Pract Endocrinol Metab. 2006;2(6):300-301.
68. Poynten AM, Gan SK, Kriketos AD, et al. Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content. Metabolism. 2003;52(6):699-704.
69. Alvarsson M, Grill V. Impact of nicotinic acid treatment on insulin secretion and insulin sensitivity in low and high insulin responders. Scan J Clin Lab Invest. 1996;56:563-570.
70. Preiss D, Sattar N. Statins and the risk of new-onset diabetes: a review of recent evidence. Curr Opin Lipidol. 2011;22(6):460-466.
71. Backes JM, Gibson CA, Howard PA. Optimal lipid modification: the rationale for combination therapy. Vasc Health Risk Manag. 2005;1(4): 317-331.
72. Niaspan [package insert]. North Chicago, IL: Abbott Laboratories; 2010.
73. Knopp RH, Alagona P, Davidson M, et al. 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(9):1097-1104.
74. Alsheikh-Ali AA, Karas RH. The safety of niacin in the US Food and Drug Administration adverse event reporting database. Am J Cardiol. 2008;101(8A):9B-13B.
75. McKenney JM, Jones PH, Bays HE, et al. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis. 2007;192(2):432-437.
76. Knopp RH, Retzlaff BM, Fish B, et al. The SLIM study: Slo-Niacin®and atorvastatin treatment of lipoproteins and inflammatory markers in combined hyperlipidemia. J Clin Lipidol. 2009;3(3):167-178.
77. Harikrishnan S, Rajeev E, Tharakan JA, et al. Efficacy and safety of combination of extended release niacin and atorvastatin in patients with low levels of high density lipoprotein cholesterol. Indian Heart J. 2008;60(3):215-222.
78. Sang ZC, Wang F, Zhou Q, et al. Combined use of extended-release niacin and atorvastatin: safety and effects on lipid modification. Chin Med J (Engl). 2009;122(14):1615-1620.
79. Moore A, Phan BA, Challender C, Williamson J, Marcovina S, Zhao XQ. Effects of adding extended-release niacin and colesevelam to statin therapy on lipid levels in subjects with atherosclerotic disease. J Clin Lipidol. 2007;1(6):620-625.
80. Latry P, Molimard M, Dedieu B, Couffinhal T, Begaud B, Martin-Latry K. Adherence with statins in a real-life setting is better when associated cardiovascular risk factors increase: a cohort study. BMC Cardiovasc Disord. 2011;11(1):46.
81. Petersen SE, Irvine D, Wise L. Trends in statin prescription in the UK 2002-2008. Demographics and determinants of non-adherence. Pharmacoepidemiol Drug Saf. 2010;19(suppl 1):S32.
82. Benner JS, Tierce JC, Ballantyne CM, et al. Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy. Pharmacoeconomics. 2004;22(suppl 3):13-23.
83. Kardas P. How to improve patient compiance with lipid lowering medication? Atherosclerosis Suppl. 2009;10(2):e941. Abstract P766.
84. Polinski J, Patorno E, Desai A, et al. Drug burden as a predictor of adherence to a newly prescribed statin. Pharmacoepidemiol Drug Saf. 2010;19(suppl 1):S57.
85. MacLean EA, Perry BM, Possidente C, Mardekian J, Sanchez R. Evaluation of adherence and persistence among high potency statin users in Massachusetts. J Manag Care Pharm. 2009;15(7):582.
86. Molokhia M, McKeigue P, Curcin V, Majeed A. Statin induced myopathy and myalgia: time trend analysis and comparison of risk associated with statin class from 1991-2006. PLoS One. 2008;3(6):e2522.
87. Jacobson TA. A "hot" topic in dyslipidemia management-"how to beat a flush": optimizing niacin tolerability to promote long-term treatment adherence and coronary disease prevention. Mayo Clin Proc. 2010;85(4):365-379.