Long-Term Safety and Efficacy of a Combination of Niacin Extended Release and Simvastatin in Patients with Dyslipidemia
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
High-dose HMG-CoA reductase inhibitors (statins) fail to prevent approximately two-thirds of cardiovascular events. This fact has focused increased attention on treating abnormalities of non-high-density lipoprotein-cholesterol (non-HDL-C), HDL-C, and triglycerides in national guidelines and has intensified interest in combination therapy.
The OCEANS study (Open-label evaluation of the safety and efficacy of a Combination of niacin ER and simvAstatin in patieNts with dySlipidemia; ClinicalTrials.gov identifier: NCT00080275) evaluated the safety and efficacy of a combination of niacin extended release and simvastatin (NER/S; SIMCOR®) over 52 weeks in 520 patients with mixed dyslipidemia. After a ≥4-week run-in phase of diet modification and simvastatin 40 mg/day, median baseline values (mg/dL) were: non-HDL-C = 141, low-density lipoprotein-cholesterol (LDL-C) =110, HDL-C = 45, and triglyceride = 151. Patients were randomized to an 8- or 12-week niacin titration scheme to a maximum NER/S dosage of 2000/40 mg/day.
Differences between titration groups in tolerability, safety, and efficacy were minimal; therefore, all results are for pooled titration groups. The safety of NER/S was consistent with the safety profile of each individual component. Treatment with NER/S was well tolerated: 71% of patients experienced flushing and 92% of flushing episodes were mild or moderate in intensity. Overall, 61 % of patients experienced flushing episodes that were rated as mild or moderate in intensity. Flushing decreased over time: <40% of those who had flushing during titration experienced flushing during the final 12 weeks. A total of 20% of patients discontinued treatment because of a treatment-related adverse event, including 7% who discontinued because of flushing. Median changes from baseline (following the simvastatin 40 mg/day run-in phase) to 24 weeks were: non-HDL-C = −27.3%, LDL-C = −25.0%, HDL-C = +23.9%, and triglycerides = −35.9% (all p < 0.0001 vs baseline). In lipid-treatment-naive patients, NER/S 2000/40 mg/day decreased non-HDL-C, LDL-C, and triglycerides by approximately 50% and increased HDL-C by approximately 25% when week-24 lipid values were compared with lipid values obtained prior to the simvastatin 40 mg/day run-in. All three therapeutic lipid targets (LDL-C [risk-adjusted goal], HDL-C ≥40 mg/dL, and triglycerides <150 mg/dL) were achieved concurrently by 65% of patients treated with NER/S.
Treatment with NER/S 2000/40 mg/day is well tolerated, has no unanticipated adverse events, and provides additional, clinically relevant improvements in multiple lipid parameters beyond statin monotherapy.
- LaRosa, J.C., Jiang, H., Suma, V. (1999) Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA 24: pp. 2340-6 CrossRef
- 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 285: pp. 2486-97 CrossRef
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet 360: pp. 7-22 CrossRef
- 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 106: pp. 3143-421
- Grundy, S.M., Cleeman, J.I., Merz, C.N.B. (2004) Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 110: pp. 227-39 CrossRef
- Hsia, S.H. (2003) Non-HDL cholesterol: into the spotlight. Diabetes Care 26: pp. 240-2 CrossRef
- Brown, G.B., Stukovsky, K.H., Zhao, X.Q. (2006) 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 17: pp. 631-6 CrossRef
- Davidson, M.H., Maki, K.C., Pearson, T.A. (2005) Results of the National Cholesterol Education (NCEP) program evaluation project utilizing novel e-technology (NEPTUNE) II survey and implications for treatment under the recent NCEP writing group recommendations. Am J Cardiol 96: pp. 556-63 CrossRef
- Evaluation of the safety & efficacy of a combination of niacin ER & simvastatin in patients with dyslipidemia (OCEANS) [ClinicalTrials.gov identifier: NCT00080275]. ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT00080275 [Accessed 2008 Feb 28].
- Allain, C.C., Poon, L., Chan, S.G. (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20: pp. 470-5
- Cole, T.G., Ferguson, C.A., Gibson, D.W. (2001) Optimization of ß-quantification methods for high-throughput applications. Clin Chem 47: pp. 712-21
- Friedewald, W.T., Levy, R.I., Fredrickson, D.S. (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma without the use of the ultracentrifuge. Clin Chem 18: pp. 449-502
- Kohlmeier, M. (1986) Direct enzymic measurement of glycerides in serum and in lipoprotein fractions. Clin Chem 32: pp. 63-6
- Warnick, G.R., Benderson, J. (1982) Dextran sulfate-Mg2+ precipitation procedure for quantification of high-density-lipoprotein cholesterol. Clin Chem 28: pp. 1379-88
- Autokit Apo A-1: code no. 991-27201 [product insert]. Rev. #1/9603IBD002K. Osaka: WakoPure Chemical Industries, Ltd; 1996.
- Autokit Apo B: code no. 993-27401 [product insert]. Rev. #1/9603IBD002K. Osaka: WakoPure Chemical Industries, Ltd; 1996.
- Autokit Lp(a): code no. 995-41901 [product insert]. Rev. #l/9903IBD00K. Osaka: WakoPure Chemical Industries, Ltd; 1999.
- Brown, B.G., Zhao, X.Q., Chait, A. (2001) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 345: pp. 1583-92 CrossRef
- Taylor, A.J., Sullenberger, L.E., Lee, H.J. (2004) 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: pp. 3512-7 CrossRef
- Taylor, A.J., Lee, H.J., Sullenberger, L.E. (2006) The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin 22: pp. 2243-50 CrossRef
- McKenney, J.M., Jones, P.H., Bays, H.E. (2007) 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 192: pp. 432-7 CrossRef
- Rubenfire, M. (2004) 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 Group. Am J Cardiol 94: pp. 306-11 CrossRef
- Garg, A., Grundy, S.M. (1990) Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 264: pp. 723-6 CrossRef
- Elam, M.B., Hunninghake, D.B., Davis, K.B. (2000) 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 284: pp. 1263-70 CrossRef
- Grundy, S.M., Vega, G.L., McGovern, M.E. (2002) Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes. Arch Intern Med 162: pp. 1568-76 CrossRef
- Robinson, J.G., Davidson, M.H. (2006) Combination therapy with ezetimibe and simvastatin to achieve aggressive LDL reduction. Expert Rev Cardiovasc Ther 4: pp. 461-76 CrossRef
- Karas, R., Cziraky, M., Quimbo, R. (2006) Cardiovascular event reduction associated with achieving optimal values multiple lipids [abstract]. Circulation 114: pp. 898
- Niacin plus statin to prevent vascular events [ClinicalTrials.gov identifier: NCT00120289]. ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT00120289 [Accessed 2008 Feb 28].
- Long-Term Safety and Efficacy of a Combination of Niacin Extended Release and Simvastatin in Patients with Dyslipidemia
American Journal of Cardiovascular Drugs
Volume 8, Issue 2 , pp 69-81
- Cover Date
- Print ISSN
- Online ISSN
- Springer International Publishing
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Division of Cardiology, Molecular Cardiology Research Institute, Tufts Medical Center, 800 Washington Street, Box 80, Boston, Massachusetts, 02111, USA
- 2. Department of Veterans Affairs Medical Center, Atherosclerosis Research Center, Long Beach, California, USA
- 3. Division of Metabolism, Northwest Lipid Research Clinic, Endocrinology and Nutrition, University of Washington School of Medicine, Seattle, Washington, USA
- 4. Abbott, Weston, Florida, USA
- 5. Division of Cardiology, University of Chicago, Chicago, Illinois, USA