The progression of atherosclerosis, which is responsible for coronary heart disease (CHD), stroke, carotid and femoral artery stenosis (peripheral vascular disease), is associated with multiple cardiovascular disease (CVD) risk factors including hyperlipidaemia. In a process of literature review the Niche team was involved in a consideration the current evidence giving consideration to the new preprotein subtilisin kexin 9 and antisense oligonucleotide (ASO) technologies [1].
A recent genetic study in man suggests that there are 95 genetic loci associated with lipid metabolism in man, all of which are potential drug targets. In epidemiological studies a 1% reduction in low-density lipoprotein cholesterol (LDL-C) is associated with a 1% reduction in cardiovascular events and a 1% increase in high-density lipoprotein cholesterol (HDL-C) is associated with a 3% reduction in events. The data on triglycerides, triglyceride-rich remnants, small dense lipoprotein subfractions and lipoprotein (a) are less clear but all are associated with increased risk. Statins are acknowledged first-line drugs for most lipid disorders but do not address all CVD disease risk. At least part of this ‘residual risk’ may be attributable to dyslipidaemia. Common use of statins has also exposed a group where their use is limited by side effects. Discontinuation of therapy is seen in about 5% of patients receiving statins or fibrates and 30% in the case of bile acid sequestrants. The importance of hyperlipidaemia as a problem means it is an active area for drug development. Many of the targets identified almost a decade ago still remain but new themes have emerged with the discovery of preprotein subtilisin kexin 9 as a control system for the LDL receptor and with the development of antisense oligonucleotide (ASO) technology.
Our reviews were based on PubMed searches conducted by the Niche team for each major drug class listed for trials of compounds in man for hyperlipidaemia (cholesterol, triglycerides, LDL-C, HDL-C) allied with searches of ClinicalTrials.gov, medical abstracts services (MedScape), financial analytical reports on the lipid-lowering drugs (Reuters, Forbes, DataMonitor), and individual pharmaceutical company websites and press releases up to 14 November 2011. We have subsequently generated several publications from the research [2-4].
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