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.
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.
Stein
Evan A
EA
Metabolic & Atherosclerosis Research Center, Cincinnati, Ohio, USA. esteinmrl@aol.com
Ballantyne
Christie M
CM
Windler
Eberhard
E
Sirnes
Per Anton
PA
Sussekov
Andrey
A
Yigit
Zerrin
Z
Seper
Claudia
C
Gimpelewicz
Claudio R
CR
D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D002784:Cholesterol / Q000097:blood; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy*; D000069438:Ezetimibe; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D007211:Indoles / Q000008:administration & dosage*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D003692:Delayed-Action Preparations; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008074:Lipoproteins; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D000069438:Ezetimibe