Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins

Am J Cardiol. 2008 Feb 15;101(4):490-6. doi: 10.1016/j.amjcard.2007.09.099. Epub 2007 Dec 20.

Abstract

Although statin treatment is generally well tolerated, it is estimated that 5% to 10% of patients develop muscle-related side effects (MRSEs), resulting in less effective nonstatin alternatives or cessation of lipid-lowering therapy completely. This study was designed to assess the efficacy and tolerability of extended-release fluvastatin (fluvastatin XL) and ezetimibe alone or in combination in patients with previous MRSEs with other statins. This was a double-blinded, double-dummy trial of 199 mostly moderate- or high-risk dyslipidemic patients randomized to fluvastatin XL 80 mg/day (n = 69), ezetimibe 10 mg/day (n = 66), or fluvastatin XL 80 mg/day plus ezetimibe 10 mg/day (n = 64) for 12 weeks. Fluvastatin XL lowered low-density lipoprotein (LDL) cholesterol by 32.8% compared with 15.6% with ezetimibe (between-group difference -17.1%, 95% confidence interval -23.6 to -10.7, p <0.0001); the fluvastatin XL/ezetimibe combination lowered LDL cholesterol by 46.1% (between-group difference vs ezetimibe -30.4%, 95% confidence interval -37.0 to -23.8, p <0.0001). Proportions of patients achieving their National Cholesterol Education Program Adult Treatment Panel III target LDL cholesterol were 84% with the fluvastatin XL/ezetimibe combination, 59% with fluvastatin XL, and 29% with ezetimibe (p <0.001 for fluvastatin XL monotherapy or combination therapy vs ezetimibe monotherapy). Incidences of MRSEs were 24% in the ezetimibe group, 17% in the fluvastatin XL group, and 14% in the combination group. There were no instances of creatine kinase increases >or=10 times upper limit of normal. In conclusion, in patients with a history of statin-associated MRSEs, fluvastatin XL alone or in combination with ezetimibe offers an effective and well-tolerated lipid-lowering option.

Trial registration: ClinicalTrials.gov NCT00125125.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / administration & dosage*
  • Azetidines / administration & dosage*
  • Cholesterol / blood
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias / drug therapy*
  • Ezetimibe
  • Fatty Acids, Monounsaturated / administration & dosage*
  • Female
  • Fluvastatin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Indoles / administration & dosage*
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Muscular Diseases / chemically induced
  • Treatment Outcome
  • Triglycerides / blood

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Delayed-Action Preparations
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Lipoproteins
  • Triglycerides
  • Fluvastatin
  • Cholesterol
  • Ezetimibe

Associated data

  • ClinicalTrials.gov/NCT00125125