Clinical rationale for rosuvastatin, a potent new HMG-CoA reductase inhibitor

Coronary heart disease (CHD) is the leading cause of death worldwide, and e ffective treatment of hyperlipidaemia can prevent development of CHD and si gnificantly reduce the risk for cardiovascular events and mortality in this disease. The advent of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) red uctase inhibitors (statins) has revolutionised the treatment of hyperlipida emia, but many patients receiving these drugs still do not achieve their th erapeutic goals. Rosuvastatin (Crestor(TM); formerly ZD4522) is a new, pote nt and long-lasting inhibitor of HMG-CoA reductase that is highly selective for hepatocytes. Its pharmacokinetics permit once-daily dosing, and a lack of oxidative hepatic metabolism results in a reduced potential for drug-dr ug interactions. Preliminary clinical results indicate that it produces rap id dose-related reductions in total cholesterol, low-density lipoprotein ch olesterol, triglycerides, and apolipoprotein B that may exceed those achiev ed with other currently available statins. Increases in high-density lipopr otein cholesterol have also been observed. Rosuvastatin is also well tolera ted, with no evidence of either hepato- or myotoxicity. It is hoped that ne w agents such as rosuvastatin may help to reduce the high global morbidity, mortality and associated costs of CHD and related vascular disorders.