title: Combination therapy with fluvastatin and niacin in hypercholesterolemia: a preliminary report on safety.
abstract: A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303.
authors.forename: T A
authors.initials: TA
authors.lastname: Jacobson
authors.forename: L F
authors.initials: LF
authors.lastname: Amorosa
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D013997:Time Factors
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D008074:Lipoproteins; D009525:Niacin; D000077340:Fluvastatin