Critical appraisal of the role of pitavastatin in treating dyslipidemias and achieving lipid goals

Abstract

Pitavastatin is a potent HMG-CoA reductase inhibitor and efficient hepatocyte low-density lipoprotein cholesterol (LDL-C) receptor inducer, producing robust reduction of the serum LDL-C levels, even at a low dose. Pitavastatin and its lactone form are minimally metabolized by CYP enzymes, and are therefore associated with minimal drug-drug interactions (DDIs). Pitavastatin 2 to 4 mg has potent LDL-C-reducing activity, equivalent to that of atorvastatin 10 to 20 mg; several clinical trials have revealed consistently superior high-density lipoprotein cholesterol (HDL-C) elevating activity of pitavastatin than that of atorvastatin. Pitavastatin-induced HDL-C elevation has been shown to be sustained, even incremental, in long-term clinical trials. Pitavastatin was as well-tolerated as atorvastatin or simvastatin in double-blind randomized clinical trials. Two-year long-term safety and effectiveness of pitavastain has been confirmed in a large-scale, prospective post-marketing surveillance. The safety and efficacy profile of pitavastatin is favorable for the treatment of dyslipidemia, especially in metabolic syndrome patients. In addition to control of LDL-C, adequate control of triglyceride (TG) and HDL-C, hypertension and hyperglycemia is also necessary in metabolic syndrome patients. Pitavastatin produces adequate control of LDL-C and TG, along with potent and incremental HDL-C elevation, with a low frequency of DDIs.

Keywords: HMG-CoA reductase inhibitor; drug–drug interaction; efficacy; pitavastatin; safety.

Figure 1

Chemical structure of pitavastatin.

Figure 2

Binding image of pitavastatin and HMG-CoA reductase.

Figure 3

Metabolic pathway of pitavastatin. Adapted with permission from Fujino H, Yamada I, Shimada S, et al. Metabolic fate of pitavastatin, a new inhibitor of HMG-CoA reductase: human UDP-glucuronosyltransferase enzymes involved in lactonization. Xenobiotica. 2003;33(1):27–41; Fujino H, Saito T, Tsunenari Y, et al. Metabolic properties of the acid and lactone forms of HMG-CoA reductase inhibitors. Xenobiotica. 2004;34(11–12):961–971. Copyright © 2003, 2004 Taylor & Francis. Abbreviation: Glu-, monoglucuronic acid conjugate.

Figure 4

95% confidence interval on treatment difference in adjusted mean percentage change in LDL-C observed in phase III double-blind clinical trial of pitavastatin vs atorvastatin. Note: Non-inferiority margin of LDL-C reduction by pitavastatin to that by atorvastatin was set to −6%.

Figure 5

Time course of mean HDL-C over 52 weeks in a long-term study of pitavastatin. Note: Parentheses, number of patients.

Figure 6

Cumulative incidence of adverse drug reactions by Kaplan-Meier method in LIVES study. Modified from Kurihara et al.