Long-term treatment with pitavastatin (NK-104), a new HMG-CoA reductase inhibitor, of patients with heterozygous familial hypercholesterolemia.
The clinical efficacy and safety of pitavastatin (NK-104), a novel HMG-CoA reductase inhibitor, during long-term treatment, were examined in 25 patients (male/female=11/14, mean age=53+/-13 (mean+/-SD) years) with heterozygous familial hypercholesterolemia (FH). After a period on placebo of >4 weeks, 2 mg/day of pitavastatin was administered for 8 weeks, and the dose was increased to 4 mg/day for up to 104 weeks. Total cholesterol (TC) decreased by 31% from the initial value of 340+/-57 to 237+/-40 mg/dl (P<0.0001) at week 8. During treatment with the higher dose, TC decreased even further to 212+/-35 mg/dl at week 12; it decreased by 37% from the initial value (P<0.0001). Similarly, the baseline low-density lipoprotein (LDL)-cholesterol (LDL-C) decreased by 41% at week 8, and by 49% at week 12, from 267+/-61 mg/dl at baseline. These findings indicate a dose-dependent effect of the drug on TC and LDL-C concentrations. To examine whether the levels of circulating matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of metalloproteinases: TIMPs) are altered during lipid-lowering therapy, we also measured their plasma levels. The mean levels of MMP-2 and -3 were significantly increased. No significant alteration was found in MMP-9, TIMP-1 and -2 levels. As for the safety of pitavastatin, adverse reactions were observed in one case (4%) of subjective and objective symptoms. The effects of pitavastatin on TC and LDL-C were stable during long treatment of patients with heterozygous FH.
Noji
Yoshihiro
Y
Molecular Genetics of Cardiovascular Disorders (The Second Department of Internal Medicine), Vascular Medicine, Division of Cardiovascular Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. nojinoji@im2.m.kanazawa-u.ac.jp
Higashikata
Toshinori
T
Inazu
Akihiro
A
Nohara
Atsushi
A
Ueda
Kosei
K
Miyamoto
Susumu
S
Kajinami
Kouji
K
Takegoshi
Tadayoshi
T
Koizumi
Junji
J
Mabuchi
Hiroshi
H
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001053:Apolipoproteins / Q000032:analysis; D001774:Blood Chemical Analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000032:analysis; D008077:Lipoproteins, LDL / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D011804:Quinolines / Q000008:administration & dosage*; D012016:Reference Values; D016896:Treatment Outcome; D014280:Triglycerides / Q000032:analysis
D001053:Apolipoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011804:Quinolines; D014280:Triglycerides; C108475:pitavastatin