Long-term treatment with pitavastatin (NK-104), a new HMG-CoA reductase inhibitor, of patients with heterozygous familial hypercholesterolemia.

Abstract

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.

• Authors: Yoshihiro Noji, Toshinori Higashikata, Akihiro Inazu, Atsushi Nohara, Kosei Ueda, Susumu Miyamoto, Kouji Kajinami, Tadayoshi Takegoshi, Junji Koizumi, Hiroshi Mabuchi, Hokuriku NK-104 Study Group
• Journal: Atherosclerosis (Atherosclerosis) Vol. 163 Issue 1 Pg. 157-64 (Jul 2002) ISSN: 0021-9150 [Print] Ireland
• PMID: 12048134 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article)

Chemical References

• Apolipoproteins
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipoproteins, HDL
• Lipoproteins, LDL
• Quinolines
• Triglycerides
• pitavastatin

Topics

• Adult
• Aged
• Analysis of Variance
• Apolipoproteins (analysis)
• Blood Chemical Analysis
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Heterozygote
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage)
• Hyperlipoproteinemia Type II (drug therapy, genetics)
• Lipoproteins, HDL (analysis)
• Lipoproteins, LDL (analysis)
• Male
• Middle Aged
• Normal Distribution
• Quinolines (administration & dosage)
• Reference Values
• Treatment Outcome
• Triglycerides (analysis)