Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials

Metabolism: Clinical and Experimental

Volumn 65, Issue 11, 2016, Pages 1664-1678

  Sahebkar, Amirhosssein ^a,b   Reiner, Željko ^c   Simental Mendía, Luis E ^d   Ferretti, Gianna ^e   Cicero, Arrigo F G ^f  

^a MASHHAD UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c KBC Zagreb   (Croatia)

^d INSTITUTO MEXICANO DEL SEGURO SOCIAL   (Mexico)

^e UNIVERSITÀ POLITECNICA DELLE MARCHE   (Italy)

^f UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Extended release niacin; Lipoprotein(a); Meta analysis; Systematic review

Indexed keywords

HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPOPROTEIN A; NICOTINIC ACID; ANTILIPEMIC AGENT; DELAYED RELEASE FORMULATION;

ARTICLE; CAROTID ATHEROSCLEROSIS; CONTROLLED DRUG RELEASE; DRUG BLOOD LEVEL; DRUG EFFECT; DYSLIPIDEMIA; EXTENDED DRUG RELEASE; HUMAN; LIMIT OF QUANTITATION; LIPOPROTEIN BLOOD LEVEL; META ANALYSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SLOW DRUG RELEASE; SUSTAINED DRUG RELEASE; SYSTEMATIC REVIEW; TREATMENT DURATION; BLOOD; DELAYED RELEASE FORMULATION; DIETARY SUPPLEMENT;

DELAYED-ACTION PREPARATIONS; DIETARY SUPPLEMENTS; HUMANS; HYPOLIPIDEMIC AGENTS; LIPOPROTEIN(A); NIACIN; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84987920104     PISSN: 00260495     EISSN: 15328600     Source Type: Journal    
DOI: 10.1016/j.metabol.2016.08.007     Document Type: Article

References (69)

1. [1] Lamon-Fava, S, Diffenderfer, MR, Marcovina, SM, Lipoprotein(a) metabolism. Curr Opin Lipidol 25:3 (2014), 189–193.
2. [2] Riches, K, Porter, KE, Lipoprotein(a): cellular effects and molecular mechanisms. Cholesterol, 2012, 2012, 923289.
3. [3] Nordestgaard, BG, Chapman, J, Ray, K, Borén, J, Andreotti, F, Watts, GF, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 23 (2010), 2844–2853.
4. [4] Emerging Risk Factors Collaboration, Erqou, S, Kaptoge, S, Perry, PL, Di Angelantonio, E, Thompson, A, et al. Lipoprotein(a) concentrations and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302 (2009), 412–423.
5. [5] Derosa, G, Cicero, AF, Gaddi, A, Mugellini, A, Ciccarelli, L, Fogari, R, The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. Clin Ther 25:5 (2003), 1429–1439.
6. [6] Sirtori, CR, Calabresi, L, Ferrara, S, Pazzucconi, F, Bondioli, A, Baldassarre, D, et al. L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a). Nutr Metab Cardiovasc Dis 10 (2000), 247–251.
7. [7] Sahebkar, A, Simental-Mendía, LE, Stefanutti, C, Pirro, M, Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: a systematic review and meta-analysis. Pharmacol Res 105 (2016), 198–209.
8. [8] Akaike, M, Azuma, H, Kagawa, A, Matsumoto, K, Hayashi, I, Tamura, K, et al. Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients with atherosclerotic diseases. Clin Chem 48 (2002), 1454–1459.
9. [9] Soma, MR, Osnago-Gadda, I, Paoletti, R, Fumagalli, R, Morrisett, JD, Meschia, M, et al. The lowering of lipoprotein(a) induced by estrogen plus progesterone replacement therapy in postmenopausal women. Arch Intern Med 153 (1993), 1462–1468.
10. [10] Pan, J, Van, JT, Chan, E, Kesala, RL, Lin, M, Charles, MA, Extended-release niacin treatment of the atherogenic lipid profile and lipoprotein(a) in diabetes. Metabolism 51 (2002), 1120–1127.
11. [11] Reiner, Ž, PCSK9 inhibitors – past, present and future. Expert Opin Drug Metab Toxicol 2 (2015), 1–5.
12. [12] Cicero, AF, Colletti, A, Borghi, C, Profile of evolocumab and its potential in the treatment of hyperlipidemia. Drug Des Develop Ther 9 (2015), 3073–3082.
13. [13] Reiner, Ž, Management of patients with familial hypercholesterolaemia. Nat Rev Cardiol 12 (2015), 565–575.
14. [14] Perk, J, De Backer, G, Gohlke, H, Graham, I, Reiner, Z, Verschuren, M, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J 33 (2012), 1635–1701.
15. [15] Catapano, AL, Reiner, Z, De Backer, G, Graham, I, Taskinen, MR, Wiklund, O, et al. ESC/EAS guidelines for the management of dyslipidaemias the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 217:1 (2011), 3–46.
16. [16] Guyton, JR, Goldberg, AC, Kreisberg, RA, Sprecher, DL, Superko, HR, O'Connor, CM, Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol 82 (1998), 737–743.
17. [17] Malik, S, Kashyap, ML, Niacin, lipids, and heart disease. Curr Cardiol Rep 5 (2003), 470–476.
18. [18] 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 110 (2004), 3512–3517.
19. [19] Brown, BG, Zhao, XQ, Chait, A, Fisher, LD, Cheung, MC, Morse, JS, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 345 (2001), 1583–1592.
20. [20] Bruckert, E, Labreuche, J, Amarenco, P, Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 210:2 (2010), 353–361.
21. [21] Turner, T, Stein, EA, Non-statin treatments for managing LDL cholesterol and their outcomes. Clin Ther 37:12 (2015), 2751–2769.
22. [22] Moher, D, Liberati, A, Tetzlaff, J, Altman, DG, PRISMA Group, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ, 339, 2009, b2535, 10.1136/bmj.b2535.
23. [23] Higgins, J.P.T., Green, S., (eds.) Cochrane handbook for systematic reviews of interventions. Version 5.0.2, 2009, The Cochrane Collaboration, London.
24. [24] Borenstein, M, Hedges, L, Higgins, J, Comprehensive meta-analysis version 2. 2005, Biostat, Englewood NJ.
25. [25] Hozo, SP, Djulbegovic, B, Hozo, I, Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol, 5, 2005, 13.
26. [26] Ferretti, G, Bacchetti, T, Sahebkar, A, Effect of statin therapy on paraoxonase-1 status: a systematic review and meta-analysis of 25 clinical trials. Prog Lipid Res 60 (2015), 50–73.
27. [27] Sahebkar, A, Serban, MC, Mikhailidis, DP, Toth, PP, Muntner, P, Ursoniu, S, et al. Head-to-head comparison of statins versus fibrates in reducing plasma fibrinogen concentrations: a systematic review and meta-analysis. Pharmacol Res 103 (2016), 236–252.
28. [28] Duval, S, Tweedie, R, Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56 (2000), 455–463.
29. [29] Goldberg, A, Alagona, P, Capuzzi, DM, Guyton, J, Morgan, JM, Rodgers, J, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 85:9 (2000), 1100–1105.
30. [30] Knopp, RH, Alagona, P, Davidson, M, Goldberg, AC, Kafonek, SD, Kashyap, 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 47:9 (1998), 1097–1104.
31. [31] Superko, HR, McGovern, ME, Raul, E, Garrett, B, Differential effect of two nicotinic acid preparations on low-density lipoprotein subclass distribution in patients classified as low-density lipoprotein pattern A, B, or I. Am J Cardiol 94:5 (2004), 588–594.
32. [32] Insull, W, McGovern, ME, Schrott, H, Thompson, P, Crouse, JR, Zieve, F, et al. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Arch Intern Med 164:10 (2004), 1121–1127.
33. [33] Airan-Javia, SL, Wolf, RL, Wolfe, ML, Tadesse, M, Mohler, E, Reilly, MP, Atheroprotective lipoprotein effects of a niacin-simvastatin combination compared to low- and high-dose simvastatin monotherapy. Am Heart J 157:4 (2009), 687.e1–687.e8.
34. [34] Albers, JJ, Slee, A, O'Brien, KD, Robinson, JG, Kashyap, ML, Kwiterovich, PO, et al. Relationship of apolipoproteins A-1 and b, and lipoprotein(a) to cardiovascular outcomes: the aim-high trial (atherothrombosis intervention in metabolic syndrome with low HDL/high triglyceride and impact on global health outcomes). J Am Coll Cardiol 62:17 (2013), 1575–1579.
35. [35] Bays, HE, Brinton, EA, Triscari, J, Chen, E, MacCubbin, D, Maclean, AA, et al. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control. Vasc Health Risk Manag 11 (2015), 165–172.
36. [36] Bregar, U, Jug, B, Keber, I, Cevc, M, Sebestjen, M, Extended-release niacin/laropiprant improves endothelial function in patients after myocardial infarction. Heart Vessel 29:3 (2014), 313–319.
37. [37] Morgan, JM, Capuzzi, DM, Guyton, JR, A new extended-release niacin (Niaspan): efficacy, tolerability, and safety in hypercholesterolemic patients. Am J Cardiol 82:12A (1998), 29U–34U.
38. [38] Shah, S, Ceska, R, Gil-Extremera, B, Paolini, JF, Giezek, H, Vandormael, K, et al. Efficacy and safety of extended-release niacin/laropiprant plus statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Int J Clin Pract 64:6 (2010), 727–738.
39. [39] Grundy, SM, Vega, GL, McGovern, ME, Tulloch, BR, Kendall, DM, Fitz-Patrick, D, et al. 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 162:14 (2002), 1568–1576.
40. [40] Gleim, G, Liu, N, Thompson-Bell, S, McCrary Sisk, C, Pasternak, RC, Mitchel, Y, et al. Efficacy and safety profile of co-administered ER niacin/laropiprant and simvastatin in dyslipidaemia. Brit J Cardiol 16:2 (2009), 90–97.
41. [41] Kim, SH, Kim, MK, Lee, HY, Kang, HJ, Kim, YJ, Park, BJ, et al. Efficacy and tolerability of a new extended-release formulation of nicotinic acid in Korean adults with mixed dyslipidemia: an 8-week, multicenter, prospective, randomized, double-blind, and placebo-controlled trial. Clin Ther 33:10 (2011), 1357–1364.
42. [42] Meyers, CD, Kamanna, VS, Kashyap, ML, Niacin therapy in atherosclerosis. Curr Opin Lipidol 15:6 (2004), 659–665.
43. [43] Gille, A, Bodor, ET, Ahmed, K, Offermanns, S, Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol 48 (2008), 79–106.
44. [44] Lamon-Fava, S, Diffenderfer, MR, Barrett, PH, Buchsbaum, A, Nyaku, M, Horvath, KV, et al. Extended-release niacin alters the metabolism of plasma apolipoprotein (apo) A-I and apoB containing lipoproteins. Arterioscler Thromb Vasc Biol 28 (2008), 1672–1678.
45. [45] Hernandez, C, Molusky, M, Li, Y, Li, S, Lin, JD, Regulation of hepatic apoC3 expression by PGC-1 beta mediates hypolipidemic effect of nicotinic acid. Cell Metab 12 (2010), 411–419.
46. [46] HPS2-THRIVE Collaborative Group, Landray, MJ, Haynes, R, Hopewell, JC, Parish, S, Aung, T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 371:3 (2014), 203–212.
47. [47] Siniawski, D, Masson, W, Belziti, C, An updated meta-analysis and meta-regression of niacin in cardiovascular prevention. Circulation, 130, 2014, A13041.
48. [48] Marcovina, SM, Albers, JJ, Lp(a) measurements for clinical application. J Lipid Res 57:4 (2016), 526–537.
49. [49] AIM-HIGH Investigators, Boden, WE, Probstfield, JL, Anderson, T, Chaitman, BR, Desvignes-Nickens, P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. New Engl JMed 365:24 (2011), 2255–2256.
50. [50] Toth, PP, Murthy, AM, Sidhu, MS, Boden, WE, Is HPS2-THRIVE the death knell for niacin?. J Clin Lipidol 9:3 (2015), 343–350.
51. [51] Panahi, Y, Khalili, N, Hosseini, MS, Abbasinazari, M, Sahebkar, A, Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med 22:5 (2014), 851–857.
52. [52] Sahebkar, A, Watts, GF, New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect?. Cardiovasc Drugs Ther 27:6 (2013), 559–567.
53. [53] Sahebkar, A, Watts, GF, New LDL-cholesterol lowering therapies: pharmacology, clinical trials, and relevance to acute coronary syndromes. Clin Ther 35:8 (2013), 1082–1098.
54. [54] Kotani, K, Sahebkar, A, Serban, C, Andrica, F, Toth, PP, Jones, SR, et al. Tibolone decreases lipoprotein(a) levels in postmenopausal women: a systematic review and meta-analysis of 12 studies with 1009 patients. Atherosclerosis 242:1 (2015), 87–96.
55. [55] Serban, MC, Sahebkar, A, Mikhailidis, DP, Toth, PP, Jones, SR, Muntner, P, et al. Impact of L-carnitine on plasma lipoprotein(a) concentrations: a systematic review and meta-analysis of randomized controlled trials. Sci Rep, 6, 2016, 19188.
56. [56] Kolski, B, Tsimikas, S, Emerging therapeutic agents to lower lipoprotein(a) levels. Curr Opin Lipidol 23:6 (2012), 560–568.
57. [57] Jaeger, BR, Richter, Y, Nagel, D, Heigl, F, Vogt, A, Roeseler, E, et al. Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Pract Cardiovasc Med 6 (2009), 229–239.
58. [58] Teo, KK, Goldstein, LB, Chaitman, BR, Grant, S, Weintraub, WS, Anderson, DC, et al. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the atherothrombosis intervention in metabolic syndrome with low HDL/high triglycerides: impact on global health outcome (AIM-HIGH) trial. Stroke 44:10 (2013), 2688–2693.
59. [59] Hu, M, Yang, YL, Masuda, D, Yamashita, S, Tomlinson, B, Effect of extended-release niacin/laropiprant combination on plasma adiponectin and insulin resistance in Chinese patients with dyslipidaemia. Dis Markers, 2015, 2015, 154014.
60. [60] Julius, U, Fischer, S, Nicotinic acid as a lipid-modifying drug – a review. Atheroscler Suppl 14:1 (2013), 7–13.
61. [61] Krempler, F, Kostner, G, Bolzano, K, Sandhofer, F, Lipoprotein(a) is not a metabolic product of other lipoproteins containing apolipoprotein B. Biochim Biophys Acta 575 (1979), 63–70.
62. [62] White, AL, Lanford, RE, Cell-surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes. J Biol Chem 269 (1994), 28716–28723.
63. [63] Ooi, W, Watts, G, Chan, D, Pang, J, Tenneti, VS, Hamilton, SJ, et al. Effects of extended-release niacin on the postprandial metabolism of Lp(a) and apoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 35:12 (2015), 2686–2693.
64. [64] Ding, Y, Li, Y, Wen, A, Effect of niacin on lipids and glucose in patients with type 2 diabetes: a meta-analysis of randomized, controlled clinical trials. Clin Nutr 34:5 (2015), 838–844.
65. [65] Cenarro, A, Puzo, J, Ferrando, J, Mateo-Gallego, R, Bea, AM, Calmarza, P, et al. Effect of nicotinic acid/laropiprant in the lipoprotein(a) concentration with regard to baseline lipoprotein(a) concentration and LPA genotype. Metabolism 63:3 (2014), 365–371.
66. [66] Hoover-Plow, J, Huang, M, Lipoprotein(a) metabolism: potential sites for therapeutic targets. Metabolism 62:4 (2013), 479–491.
67. [67] Stone, NJ, Robinson, JG, Lichtenstein, AH, Bairey Merz, CN, Blum, CB, Eckel, RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 63:25 Pt B (2014), 2889–2934.
68. [68] Streja, E, Kovesdy, CP, Streja, DA, Moradi, H, Kalantar-Zadeh, K, Kashyap, ML, Niacin and progression of CKD. Am J Kidney Dis 65:5 (2015), 785–798.
69. [69] Ganji, SH, Kashyap, ML, Kamanna, VS, Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: impact on non-alcoholic fatty liver disease. Metabolism 64:9 (2015), 982–990.