title: Long-term safety and efficacy of a combination of niacin extended release and simvastatin in patients with dyslipidemia: the OCEANS study.
abstract: BACKGROUND
  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 >or=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 2,000/40 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 2,000/40 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 >or=40 mg/dL, and triglycerides <150 mg/dL) were achieved concurrently by 65% of patients treated with NER/S.
  
  
  CONCLUSIONS
  Treatment with NER/S 2,000/40 mg/day is well tolerated, has no unanticipated adverse events, and provides additional, clinically relevant improvements in multiple lipid parameters beyond statin monotherapy.
authors.affiliation: Division of Cardiology, Molecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA. rkaras@tuftsmedicalcenter.org
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
authors.forename: Robert H
authors.initials: RH
authors.lastname: Knopp
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Keller
authors.forename: Daiva R
authors.initials: DR
authors.lastname: Bajorunas
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D009525:Niacin; D002784:Cholesterol; D019821:Simvastatin