Are All Statins the Same : Focus on the Efficacy and Tolerability of Pitavastatin
American Journal of Cardiovascular Drugs, 03/31/2011
da Silva PM - Pitavastatin, the latest addition to the statin family, produces potent and consistent beneficial effects on lipids, is well tolerated, and has a favorable pharmacokinetic profile. The combination of a potent decrease in total and low-density lipoprotein (LDL) cholesterol levels and increase in high-density lipoprotein (HDL) cholesterol levels suggest that pitavastatin may produce substantial cardiovascular protection.
- Pitavastatin is approved as adjunctive therapy to diet to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein (Apo) B, and triglycerides and to increase levels of HDL cholesterol in adult patients with primary hyperlipidemia or mixed dyslipidemia.
- Pitavastatin undergoes minimal metabolism by cytochrome P450 (CYP) enzymes and, therefore, has a low propensity for drug-drug interactions with drugs metabolized by CYP enzymes or the CYP3A4 substrate grapefruit juice.
- In clinical trials, pitavastatin potently and consistently reduced serum levels of total, LDL, and non-HDL cholesterol, and triglycerides in patients with primary hypercholesterolemia where diet and other non-pharmacological measures were inadequate.
- Mean reductions from baseline in serum total and LDL cholesterol and triglyceride levels were 21-32%, 30-45%, and 10-30%, respectively.
- A consistent trend towards increased HDL cholesterol levels of 3–10% was seen.
- Long-term extension studies show that the beneficial effects of pitavastatin are maintained for up to 2 years.
- Pitavastatin produces reductions from baseline in serum total and LDL cholesterol levels to a similar extent to those seen with the potent agent atorvastatin and to a greater extent than those seen with simvastatin or pravastatin.
- Studies comparing pitavastatin and atorvastatin have shown no significant differences in the favorable effects on lipid parameters, although pitavastatin was consistently associated with trends towards increased HDL cholesterol levels.
- Pitavastatin produces beneficial effects on lipids in patients with type 2 diabetes mellitus and metabolic syndrome without deleterious effects on markers of glucose metabolism, such as fasting blood glucose levels or proportion of glycosylated hemoglobin.
- Pitavastatin appears to exert a number of beneficial effects on patients at risk of cardiovascular events independent of lipid lowering.
- In the JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study, pitavastatin was non-inferior to atorvastatin at reducing plaque volume in patients with ACS undergoing percutaneous coronary intervention.
- Beneficial effects, including favorable effects on the size and composition of atherosclerotic plaques, improvements in cardiovascular function, and improvements in markers of inflammation, oxidative stress, and renal function, have been demonstrated in a number of small studies.
- Pitavastatin is generally well tolerated in hyperlipidemic patients with or without type 2 diabetes, with the most common treatment-related adverse events being musculoskeletal or gastrointestinal in nature.
- Increases in plasma creatine kinase levels were seen in <5% of pitavastatin recipients and the incidence of myopathy or rhabdomyolysis was extremely low.