Efficacy and safety of cerivastatin 0.8 mg in patients with hypercholesterolaemia: the pivotal placebo-controlled clinical trial. Cerivastatin Study Group.
This pivotal, multicentre, double-blind, parallel-group study evaluated the efficacy and safety of cerivastatin 0.8 mg. Patients with primary hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on an American Heart Association (AHA) Step I diet, to treatment with cerivastatin 0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by 23.9 -58.4% (6th - 95th percentile). Overall attainment of the National Cholesterol Education Program (NCEP) goal was achieved by 84% of patients receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease (CHD). In the sub-population meeting the NCEP criteria for pharmacological therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD, reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by 22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001), respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in HDL-C were dependent upon triglyceride baseline levels; in patients having baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well tolerated. The most commonly reported adverse events included headache, pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10 times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin 0.8 mg is an effective and safe treatment for patients with primary hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP-recommended levels.
Insull
W
W
Lipid Research Clinic, The Methodist Hospital, Houston, Texas 77030, USA. winsull@bcm.tmc.edu
Isaacsohn
J
J
Kwiterovich
P
P
Ra
P
P
Brazg
R
R
Dujovne
C
C
Shan
M
M
Shugrue-Crowley
E
E
Ripa
S
S
Tota
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003257:Consumer Product Safety; D003327:Coronary Disease / Q000097:blood / Q000150:complications; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D011725:Pyridines; D014280:Triglycerides; C030104:lipoprotein cholesterol; D002784:Cholesterol; C086276:cerivastatin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase