title: Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia.
abstract: Combination therapy is increasingly recommended for patients with multiple lipid disorders, especially those at high risk for coronary events. We investigated the long-term safety and effectiveness of a new drug formulation containing once-daily extended-release niacin and lovastatin. A total of 814 men and women (mean age 59 years) with dyslipidemia were enrolled in a 52-week multicenter, open-label study. We used 4 escalating doses (niacin/lovastatin in milligrams): 500/10 for the first month, 1,000/20 for the second, 1,500/30 for the third, and 2,000/40 for the fourth month through week 52. Dose-dependent effects were observed for all major lipid parameters. At week 16, mean low-density lipoprotein (LDL) cholesterol and triglycerides were reduced by 47% and 41%, respectively; mean high-density lipoprotein (HDL) cholesterol was increased by 30% (all p <0.001). LDL/HDL cholesterol and total/HDL cholesterol ratios were also decreased by 58% and 48%, respectively. These effects persisted through week 52, except for the mean increase in HDL cholesterol, which had increased to 41% at 1 year. Lipoprotein (a) and C-reactive protein also decreased in a dose-related manner (by 25% and 24%, respectively, on 2,000/40 mg; p <0.01 vs baseline). Treatment was generally well tolerated. The most common adverse event was flushing, which caused 10% of patients to withdraw. Other adverse events included gastrointestinal upset, pruritus, rash, and headache. Drug-induced myopathy did not occur in any patient. The incidence of elevated liver enzymes to >3 times the upper limit of normal was 0.5%. Once-daily niacin/lovastatin exhibits substantial effects on multiple lipid risk factors and represents a significant new treatment option in the management of dyslipidemia.
authors.affiliation: Veterans Affairs Healthcare System, Long Beach, California 90822, USA. moti.kashyap@med.va.gov
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
authors.forename: Mark E
authors.initials: ME
authors.lastname: McGovern
authors.forename: Kathleen
authors.initials: K
authors.lastname: Berra
authors.forename: John R
authors.initials: JR
authors.lastname: Guyton
authors.forename: Peter O
authors.initials: PO
authors.lastname: Kwiterovich
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Harper
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Toth
authors.forename: Laurence K
authors.initials: LK
authors.lastname: Favrot
authors.forename: Boris
authors.initials: B
authors.lastname: Kerzner
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nash
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Simmons
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000187:drug effects; D008076:Cholesterol, HDL / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D017270:Lipoprotein(a) / Q000187:drug effects; D008148:Lovastatin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D009525:Niacin; D002097:C-Reactive Protein; D008148:Lovastatin