The role of statin therapy in primary hyperlipidemia and mixed dyslipidemia

In the US, ischemic cardiovascular disease (CVD) and stroke combined are the major cause of death for all age groups older than 55 years. Preventive approaches are based on the management of all risk factors and co-morbidities. The management guidelines for the lipid risk factors focus on lowering low-density lipoprotein cholesterol (LDL-C) levels. Statins, which inhibit cholesterol synthesis via blockade of the enzyme 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, are the drug of choice for LDL-C control. Currently, there are three generic and four branded statins. Pitavastatin, the latest statin to be approved by the US Food and Drug Administration (FDA) (2009), has the lipid indications of the other statins but is not indicated for CVD risk reduction. It is available in 1 mg, 2 mg, and 4 mg doses, with the recommended starting dose of 2 mg being equivalent to 20 mg of simvastatin and 10 mg of atorvastatin, and superior to 20 mg of pravastatin. Pitavastatin 2 mg reduces LDL-C levels by 39 %, apolipoprotein B by 31 %, total cholesterol by 28 % and triglycerides by 16 %, and raises high-density lipoprotein cholesterol (HDL-C) by 6 %. In phase III clinical trials, pitavastatin 4 mg decreases LDL-C by up to 45 %. Pitavastatin has a unique metabolism, with little processing by cytochrome P450 (CYP) and none by CYP3A4, and thus it may display less CYP-mediated drug interaction than other statins. However, the FDA has determined that pitavastatin should not be taken with cyclosporine. Pitavastatin should be limited to 1 mg daily with erythromycin and 2 mg daily with rifampin. Preliminary vascular investigations have suggested benefits in line with those obtained by other statins.