PITAVASTATIN: CHARACTERISTICS, ADVANTAGES AND BENEFITS: S2.5

Managing dyslipidaemia is central to lifting this burden: each mmol/l decline in LDL cholesterol (LDL-C) reduces the risk of major vascular events by around a fifth. However, current statins have limitations that hinder statin's full potential from being realised in clinical practice, including adverse events, residual risk from factors other than LDL-C, and LDL-C levels above targets recommended in guidelines. Pitavastatin potently inhibits HMG-CoA reductase, increases lipoprotein lipase expression in adipocytes, and promotes Apo A-1 production. These actions lower concentrations of LDL-C and triglycerides, and increase HDL cholesterol (HDL-C) levels respectively. Pitavastatin undergoes biliary excretion and entero-hepatic circulation: the latter may contribute to the drug's pharmacodynamic profile. CYP2C9 and CYP2C8 interact with pita-vastatin, although metabolism by these isoenzymes is negligible. The cyclopropyl group “protects” pitavastatin from metabolism by CYP3A4, reducing the risk of interactions compared to statins extensively biotransformed by this isoenzyme. Pitavastatin's major route of biotransformation is lactionisation to an inactive metabolite and therefore, unlike some other statins, does not interact with CYP3A4 substrates. Pitavastatin does not show clinically significant interactions with CYP450 inhibitors. In Caucasians, pitavastatin is non-inferior to atorvastatin in reducing LDL-C. Over three-quarters of patients receiving pitavastatin 4 mg/day attain the European Atherosclerosis Society (EAS) LDL-C targets. Pitavastatin 4 mg/day is non-inferior to simvastatin 40 mg/day respectively. Pitavastatin produced a sustained decline in levels of LDL-C and other lipids, and maintained target attainment during long-term treatment (52 weeks). HDL-C levels rose continually during 52-weeks treatment. Pitavastatin and atorvastatin produce similar reductions in plaque volume and negative vessel remodelling. Patients aged ≥65 years are particularly prone to developing CVD. In these patients, pitavastatin reduced LDL-C levels by approximately 10% more than pravastatin. Indeed, pitavastatin was significantly more efficacious than pravastatin across a range of lipid outcomes. Pitavastatin is well tolerated with a low risk of rhabdomyolysis. During open-label treatment with pitavastatin 4 mg daily for up to 52 weeks, 4.1% of patients withdrew after developing TEAEs. However, many current statins have major limitations. Moreover, innovative treatments need to address non-LDL-C residual risk (which may be marked by high triglycerides, low HDL-C concentrations or raised Apo B: Apo A-1 ratio) and increase the proportion of patients attaining treatment targets. Pitavastatin is a novel statin that induces plaque regression and is non-inferior to atorvastatin and, on some measures, superior to simvastatin, and to pravastatin in the elderly. Pitavastatin addresses non-LDL-C risk factors, including producing reproducible and sustained increases in HDL-C levels. Pitavastatin is well tolerated; as such, pitavastatin shows distinctive pharmacokinetic and clinical profiles that should help a greater proportion of dyslipidaemic patients attain their treatment goals.