NK-104: a novel synthetic HMG-CoA reductase inhibitor

An elevated level of low-density lipoprotein (LDL)-cholesterol has been rec ognised as the most important risk factor for coronary artery disease (CAD) . Development of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (H MG-CoA) ('statins'), a rate-limiting key enzyme of cholesterol synthesis pa thway, has revolutionised the cholesterol-lowering therapy. In the last dec ade, effective primary and secondary preventive measures have been establis hed in several statin trials to prevent future events of CAD by lowering LD L-cholesterol levels. These results supported the 'lower is better' hypothe sis in the relationship between LDL-cholesterol levels and CAD. NK-104 (pit avastatin, previously named as itavastatin or nisvastatin, Kowa Company Ltd ., Tokyo) has recently been developed as a new chemically synthesised and p owerful statin. On the basis of reported data, the potency of NK-104 is dos e-dependent and appears to be equivalent to that of atorvastatin. This new statin is safe and well-tolerated in the treatment of patients with hyperch olesterolaemia. The cytochrome P450 system only slightly modifies NK-104, w hich suggests the clinical advantage of this agent, because the prevalence of clinically significant interactions with a number of other commonly used drugs can be considered to be extremely low. NK-104 can provide a new and potentially superior therapeutic agent when compared with currently availab le other statins. Randomised controlled clinical trials to assess the long- term effects of this new statin on CAD would be required.