Niacin extended-release therapy in phase III clinical trials is associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events: A pooled analysis

American Journal of Cardiovascular Drugs

Volumn 11, Issue 3, 2011, Pages 179-187

  Brinton, Eliot A ^a   Kashyap, Moti L ^b,c   Vo, Anthony N ^b,c   Thakkar, Roopal B ^d   Jiang, Ping ^d   Padley, Robert J ^d  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b VA LONG BEACH HEALTHCARE SYSTEM   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d ABBOTT LABORATORIES   (United States)

Author keywords

clinical trials; flushing; lovastatin; niacin; simvastatin

Indexed keywords

MEVINOLIN; NICOTINIC ACID; PLACEBO; SIMVASTATIN;

ADULT; AGE DISTRIBUTION; ARTICLE; CONTROLLED DRUG RELEASE; CONTROLLED STUDY; DRUG DOSE TITRATION; DRUG FORMULATION; DRUG INDUCED DISEASE; DRUG SAFETY; DRUG WITHDRAWAL; DYSLIPIDEMIA; EXTENDED DRUG RELEASE; FEMALE; FLUSHING; HUMAN; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; PATIENT COMPLIANCE; PATIENT COUNSELING; PRIORITY JOURNAL; SEX DIFFERENCE; SIDE EFFECT; TREATMENT DURATION; TREATMENT WITHDRAWAL; UNSPECIFIED SIDE EFFECT;

CLINICAL TRIALS, PHASE III AS TOPIC; DELAYED-ACTION PREPARATIONS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; DYSLIPIDEMIAS; FEMALE; FLUSHING; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPOLIPIDEMIC AGENTS; LOVASTATIN; MALE; MEDICATION ADHERENCE; MIDDLE AGED; NIACIN; SIMVASTATIN;

EID: 79957829575     PISSN: 11753277     EISSN: 1179187X     Source Type: Journal    
DOI: 10.2165/11592560-000000000-00000     Document Type: Article

References (43)

1. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterollowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005 Oct 8; 366 (9493): 1267-78
2. Gazi IF, Tsimihodimos V, Tselepis AD, et al. Clinical importance and therapeutic modulation of small dense low-density lipoprotein particles. Expert Opin Biol Ther 2007 Jan; 7 (1): 53-72 (Pubitemid 46091576)
3. Lin Y, Mousa SS, Elshourbagy N, et al. Current status and future directions in lipid management: emphasizing low-density lipoproteins, high-density lipoproteins, and triglycerides as targets for therapy. Vasc Health Risk Manag 2010; 6: 73-85
4. 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 Dec; 17 (6): 631-6 (Pubitemid 44729955)
5. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll of Cardiol 1986 Dec; 8 (6): 1245-55 (Pubitemid 17208898)
6. Kuvin JT, Dave DM, Sliney KA, et al. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am J Cardiol 2006 Sep 15; 98 (6): 743-5 (Pubitemid 44301006)
7. Superko HR, McGovern ME, Raul E, et al. 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 2004 Sep 1; 94 (5): 588-94 (Pubitemid 39165836)
8. Ganji SH, Kamanna VS, Kashyap ML. Niacin and cholesterol: role in cardiovascular disease (review)J Nutr Biochem 2003 Jun; 14 (6): 298-305 (Pubitemid 36836234)
9. Guyton JR. Niacin in cardiovascular prevention: mechanisms, efficacy, and safety. Curr Opin Lipidol 2007 Aug; 18 (4): 415-20 (Pubitemid 47051920)
10. Blankenhorn DH, Selzer RH, Crawford DW, et al. Beneficial effects of colestipol-niacin therapy on the common carotid artery: two- and four-year reduction of intima-media thickness measured by ultrasound. Circulation 1993 Jul; 88 (1): 20-8 (Pubitemid 23195428)
11. 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 Jun 15; 55 (24): 2721-6
12. Miller NH. Compliance with treatment regimens in chronic asymptomatic diseases. Am J Med 1997 Feb 17; 102 (2A): 43-9 (Pubitemid 27147947)
13. Kulkarni SP, Alexander KP, Lytle B, et al. Long-term adherence with cardiovascular drug regimens. Am Heart J 2006 Jan; 151 (1): 185-91 (Pubitemid 41815352)
14. Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascular outcomes. Circulation 2009 Jun 16; 119 (23): 3028-35
15. Kamanna VS, Ganji SH, Kashyap ML. The mechanism and mitigation of niacin-induced flushing. Int J Clin Pract 2009 Sep; 63 (9): 1369-77
16. Davidson MH. Niacin use and cutaneous flushing: mechanisms and strategies for prevention. Am J Cardiol 2008 Apr 17; 101 (8A): 14B-9B
17. Pieper JA. Understanding niacin formulations. Am J Manag Care 2002 Sep; 8 (12 Suppl.): S308-14
18. Knopp RH, Alagona P, DavidsonM, 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 Sep; 47 (9): 1097-104 (Pubitemid 28428015)
19. Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment effect of Niaspan, a controlled-release niacin, in patients with hypercholesterolemia: a placebocontrolled trial. J Cardiovasc Pharmacol Ther 1996 Jul; 1 (3): 195-202
20. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan- Gemfibrozil Study Group. Arch InternMed 2000 Apr 24; 160 (8): 1177-84 (Pubitemid 30227029)
21. Hunninghake DB, McGovern ME, Koren M, et al. A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extendedrelease and lovastatin. Clin Cardiol 2003 Mar; 26 (3): 112-8 (Pubitemid 36330859)
22. Kashyap ML, McGovern ME, Berra K, et al. Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia. Am J Cardiol 2002 Mar 15; 89 (6): 672-8 (Pubitemid 34230562)
23. Ballantyne CM, Davidson MH, McKenney J, et al. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study)Am J Cardiol 2008 May 15; 101 (10): 1428-36
24. Ballantyne CM, Davidson MH, McKenney JM, et al. Comparison of the efficacy and safety of a combination tablet of niacin extended-release and simvastatin with simvastatin 80mg monotherapy: the SEACOAST II (highdose) study. J Clin Lipidol 2008 Apr; 2 (2): 79-90 (Pubitemid 351372956)
25. Karas RH, Kashyap ML, Knopp RH, et al. Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study. Am J Cardiovasc Drugs 2008; 8 (2): 69-81 (Pubitemid 351570857)
26. Bays HE, Ballantyne C. What's the deal with niacin development: is laropiprant add-on therapy a winning strategy to beat a straight flush? Curr Opin Lipidol 2009 Dec; 20 (6): 467-76
27. Guyton JR, Simmons PD. Flushing and other dermatologic adverse events associated with extended-release niacin therapy. J Clin Lipidol 2009 Apr; 3 (2): 101-8
28. Balu S, Simko RJ, Quimbo RM, et al. Impact of fixed-dose and multi-pill combination dyslipidemia therapies on medication adherence and the economic burden of sub-optimal adherence. Curr Med Res Opin 2009 Nov; 25 (11): 2765-75
29. Kamal-Bahl SJ, Burke T, Watson D, et al. Discontinuation of lipid modifying drugs among commercially insured United States patients in recent clinical practice. Am J Cardiol 2007 Feb 15; 99 (4): 530-4 (Pubitemid 46215558)
30. Rubenfire M. Safety and compliance with once-daily niacin extended-release/ lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study.AmJ Cardiol 2004 Aug 1; 94 (3): 306-11 (Pubitemid 38962694)
31. Vogt A, Kassner U, Hostalek U, et al. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. Curr Med Res Opin 2006 Feb; 22 (2): 417-25 (Pubitemid 44296766)
32. Kamal-Bahl S,Watson DJ, Ambegaonkar BM. Patients' experiences of niacininduced flushing in clinical practice: a structured telephone interview. Clin Ther 2009 Jan; 31 (1): 130-40
33. Oberwittler H, Baccara-Dinet M. Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment. Int J Clin Pract 2006 Jun; 60 (6): 707-15 (Pubitemid 43811652)
34. Niaspan [package insert]. North Chicago (IL): Abbott Laboratories, 2005
35. Ali F, Laurin MY, Lariviere C, et al. The effect of pharmacist intervention and patient education on lipid-lowering medication compliance and plasma cholesterol levels. Can J Clin Pharmacol 2003 Fall; 10 (3): 101-6 (Pubitemid 37254374)
36. Schedlbauer A, Davies P, Fahey T. Interventions to improve adherence to lipid lowering medication. Cochrane Database of Systematic Reviews 2010; (3): 1-37
37. Niaspan Uses and Important Safety Information. Abbott Laboratories; 2009 [online]. Available from URL: http://www.heartalliance.com [Accessed 2011 Mar 10]
38. Cefali EA, Simmons PD, Stanek EJ, et al. Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation. Int J Clin Pharmacol Ther 2007 Feb; 45 (2): 78-88 (Pubitemid 46344139)
39. Thakkar RB, Kashyap ML, Lewin AJ, et al. Acetylsalicylic acid reduces niacin extended-release-induced flushing in patients with dyslipidemia. Am J Cardiovasc Drugs 2009; 9 (2): 69-79
40. Paolini JF, Mitchel YB, Reyes R, et al. Effects of laropiprant on nicotinic acidinduced flushing in patients with dyslipidemia. Am J Cardiol 2008 Mar 1; 101 (5): 625-30
41. Maccubbin D, Koren MJ, Davidson M, et al. Flushing profile of extendedrelease niacin/laropiprant versus gradually titrated niacin extended-release in patients with dyslipidemia with and without ischemic cardiovascular disease. Am J Cardiol 2009 Jul 1; 104 (1): 74-81
42. Capuzzi DM, Guyton JR, Morgan JM, et al. Efficacy and safety of an extended- release niacin (Niaspan): a long-term study. Am J Cardiol 1998 Dec 17; 82 (12A): 74U-81U; discussion 5U-6U
43. Insull Jr W, Basile JN, Vo AN, et al. Efficacy and safety of combination therapy with niacin extended-release and simvastatin versus atorvastatin in patients with dyslipidemia: the SUPREME Study. J Clin Lipidol 2009 Apr; 3 (2): 109-18