Pitavastatin: an overview of the LIVES study

Abstract

The Livalo^® (Livazo^® in Europe) Effectiveness and Safety (LIVES) study, a postmarketing surveillance trial conducted in 20,279 Japanese patients with hypercholesterolemia, is the largest trial evaluating the efficacy and safety of pitavastatin 1–4 mg/day. Elderly patients (aged ≥65 years) accounted for approximately 50% of participants, and about 75% of all patients had concomitant diseases, including hypertension and Type 2 diabetes. During 2 years of follow-up, only 10.4% of patients developed adverse drug reactions (ADRs), most of which were mild in severity. No previously unknown ADRs were identified, and laboratory abnormalities such as elevated serum creatine phosphokinase (2.74%), alanine aminotransferase (1.79%), aspartate aminotransferase (1.5%) and myalgia (1.08%) represented the most common ADRs. Importantly, the ADR incidence did not differ significantly based on either concomitant drug use or age. Furthermore, subgroup analyses of the LIVES study showed that pitavastatin has beneficial effects on renal function (increased estimated glomerular filtration rate) and glycemic control (decreased HbA_1c) in hypercholesterolemic patients with chronic kidney disease and diabetes mellitus, respectively. With regard to efficacy, there was a significant reduction in LDL-C levels by 4 weeks after the start of treatment, which remained stable throughout the study period. Pitavastatin significantly and continuously increased HDL-C over 2 years. Interestingly, the percentage increase in HDL-C was higher in patients with baseline HDL-C <40 mg/dl. Similarly, a 24.2% reduction in triglycerides was observed in patients with baseline values >150 mg/dl after 2 years of pitavastatin treatment. These outcomes have been confirmed in the LIVES extension study, a 3-year follow-up of approximately 7000 patients who were enrolled in LIVES and treated with pitavastatin for >2 years. The LIVES extension study also found that the risk of cardiovascular, cerebrovascular and sudden cardiac death events was significantly reduced in patients who achieved on-treatment HDL-C and LDL-C target levels compared with patients not achieving lipid goals. In conclusion, pitavastatin has an excellent safety profile, even in polymedicated and elderly patients and, in addition to lowering LDL-C and triglyceride levels it increases HDL-C, which may be predictive of residual cardiovascular risk among patients on lipid-lowering medications, thus providing effective and sustained improvements in the atherogenic profile.

Key Words:

• chronic kidney disease
• efficacy
• estimated glomerular filtration rate
• HbA_1c
• HDL-C n hypercholesterolemia
• LDL-C n LIVES study
• pitavastatin
• postmarketing
• safety