Our publication on new therapies to reduce low-density lipoprotein cholesterol is published today [1].

Lipid-lowering is an intervention that reduces atherosclerosis and its complications. In cardiovascular disease (CVD) outcome studies a 1 mmol/l reduction in LDL-C is associated with a 21% reduction in events. In surveys of patients at high CVD risk about 30–50% of patients do not achieve goals with current therapies. Statins currently form the standard of care but are not able to reduce low-density lipoprotein cholesterol (LDL-C) adequately in all patients – particularly those with familial hypercholesterolaemia and those with statin intolerance.

Combination therapy with statins is well established and ezetimibe is often used as an additional LDL-C lowering agent reducing LDL-C by 20%. However, its clinical efficacy remains controversial. Newer, more potent methods are being developed. Lomitapide, a microsomal transfer protein inhibitor (MTPI), and mipomersen, an antisense oligonucleotide (ASO), have been shown to improve LDL-C levels by 25–50% in patients with homozygous familial hypercholesterolaemia. In patients with heterozygous familial hypercholesterolaemia or statin intolerance antibody-based inhibitors of preprotein convertase subtilisin/kexin 9 (PCSK9) produce reductions in LDL-C of 30–65%. Cholesterol ester transfer protein inhibitors (CETPIs) reduce LDL-C by 30–40% as well as raising levels of high-density lipoprotein cholesterol (HDL-C) and may also have a role as additional LDL-C-reducing drugs.

Review of the literature confirms that surrogate outcome trials will be required with lomitapide or mipomersen to confirm their effects in homozygous familial hypercholesterolaemia and clinical endpoint trials will be needed for PCSK9 and CETPIs if these are to be adopted widely.

References

1. Wierzbicki et al. New therapies to reduce low-density lipoprotein cholesterol. Current Opin in Cardiol 2013 Jul;28(4):452-7.