Five years ago I was lucky enough to be involved in a project that resulted in publications about the then current state of the art treatments for lipid-lowering treatments [1] and the potential for the proprotein convertase subtilisin/kexin type 9 (PCSK9) axis for the treatment of hyperlipidaemia [2]. Today, over 300 people have looked at the first paper on ResearchGate. Cutting down on lipids has been shown to help lower cholesterol and its related problems. The development of atherosclerosis, which leads to coronary heart disease (CHD), stroke, and peripheral vascular disease like carotid and femoral artery stenosis, is linked to a number of risk factors for CVD, such as high cholesterol.

Statins were the mainstay of care and had done a huge amount of good for society by lowering the number of cases of atherosclerotic heart disease, but they still can't treat all parts of dyslipidaemia. Even though they were widely used, atherosclerotic cardiovascular disease was and still is the world's top cause of death.

Innovations in technology, like those in genetics, have changed the way drugs are found and made. A lot of new therapeutic substances are being made. There are more medicines for lowering bad cholesterol, like thyroid mimetics (thyroid receptor beta-agonists), antisense oligonucleotides, or microsomal transfer protein inhibitors (MTPI); lowering triglycerides, like novel peroxosimal proliferator activating receptors agonists, MTPIs, diacylglycerol acyl transferase-1 inhibitors; and lowering high-density lipoprotein cholesterol (HDL-C), like mimetic peptides; HDL delipidation strategies and cholesterol ester transfer protein inhibitors; and controlling inflammation, like phospholipase inhibitors.

Therapeutically lowering LDL-C can help stop fatty cardiovascular disease, and the size of the effect depends on how much LDL-C is lowered and how long it is exposed to the drug. This new information backs up the idea that lowering long-term LDL-C risk should be a main goal of therapy. By blocking PCSK9 with monoclonal antibodies, LDL-C levels could be lowered to very low levels.

New therapeutic platforms, like RNA inhibition, make it possible to combine strong lipid-lowering with dosing schedules that aren't repeated often. This makes medicines that work like vaccines possible. In clinical studies, alipogene tiparvovec has also been used for gene therapy to treat some rare disorders, such as lipoprotein lipase deficiency. In 2012, we said that lipid-lowering drugs are likely to continue to be an area of fast growth for new treatments because new and old chemicals may work together to treat atherosclerosis. Interest continues 5 years later, we will soon be hearing about the therapeutic potential of lipid-lowering therapies with targets other than LDL-C, such as Lp(a) [lipoprotein(a)], TRL (triglyceride-rich lipoproteins), and remnant cholesterol currently being investigated in on-going clinical trials. The available evidence suggests that reducing Lp(a) or TRLs could attenuate atherosclerotic cardiovascular disease risk in specific categories of patients.

References

1. Wierzbicki AS, Hardman TC, Viljoen A. New lipid-lowering drugs: an update. Int J Clin Pract. 2012:270-80. doi: 10.1111/j.1742-1241.2011.02867.x.
2. Wierzbicki AS, Hardman TC, Viljoen A. Inhibition of pre-protein convertase serine kexin-9 (PCSK-9) as a treatment for hyperlipidaemia. Expert Opin. Investig. Drug 2012; 21:667-676.