Modulators of dyslipidaemia

Coronary heart disease (CHD) is the leading cause of morbidity and mortality in most developed nations and atherosclerotic cardiovascular disease accounts for approximately one-half of all deaths due to CHD. Dyslipidaemias, which include various combinations of hypercholesterolaemia, hypertriglyceridaemia and hypoalphalipoproteinaemia, are major risk factors for atherosclerotic CHD. Current therapy largely treats hypercholesterolaemia, as reflected in the sales of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMGR-Is, statins) which account for a worldwide market share of 88%. The fibrates, which account for 9% of worldwide market share, effectively treat hypertriglyceridaemia but have inconsistent effects on hypercholesterolaemia and hypoalphalipoproteinaemia. Niacin, although an effective treatment for dyslipidaemias, suffers from a poor side-effect profile and therefore poor compliance. Moreover, niacin is not recommended for diabetics, a population in which atherosclerotic cardiovascular diseas...