American Journal of Cardiovascular Drugs

, Volume 8, Issue 2, pp 69–81

Long-Term Safety and Efficacy of a Combination of Niacin Extended Release and Simvastatin in Patients with Dyslipidemia

The OCEANS Study
  • Richard H. Karas
  • Moti L. Kashyap
  • Robert H. Knopp
  • Laurence H. Keller
  • Daiva R. Bajorunas
  • Michael H. Davidson
Original Research Article

DOI: 10.2165/00129784-200808020-00001

Cite this article as:
Karas, R.H., Kashyap, M.L., Knopp, R.H. et al. Am J Cardiovasc Drugs (2008) 8: 69. doi:10.2165/00129784-200808020-00001

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Richard H. Karas
    • 1
  • Moti L. Kashyap
    • 2
  • Robert H. Knopp
    • 3
  • Laurence H. Keller
    • 4
  • Daiva R. Bajorunas
    • 4
  • Michael H. Davidson
    • 5
  1. 1.Division of Cardiology, Molecular Cardiology Research InstituteTufts Medical CenterBostonUSA
  2. 2.Department of Veterans Affairs Medical CenterAtherosclerosis Research CenterLong BeachUSA
  3. 3.Division of Metabolism, Northwest Lipid Research Clinic, Endocrinology and NutritionUniversity of Washington School of MedicineSeattleUSA
  4. 4.AbbottWestonUSA
  5. 5.Division of CardiologyUniversity of ChicagoChicagoUSA

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