Pharmacological management of elevated LDL in patients with hypercholesterolemia and mixed dyslipidaemia

Low-density lipoprotein cholesterol (LDL-C) is the major lipid target to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with hypercholesterolemia and in those with mixed dyslipidemia. Lifestyle and diet modification should always be the first approach to management, but pharmacological intervention is often required.

This article discusses the current therapies to reduce LDL-C and introduces some of the new drugs in late-stage development. The articles reviewed were identified by a PubMed search up to the current time.

Statins remain the primary therapy to reduce LDL-C, but statins are often insufficient to achieve the more aggressive LDL-C targets. Ezetimibe is the next recommended therapy to add, and bempedoic acid provides another oral drug that can be added or substituted for the statins. The injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective drugs in reducing LDL-C, but their uptake has not met expectations because of issues of cost and patients' reluctance to take injection therapy. The oral PCSK9 inhibitors in development and obicetrapib appear safe and very effective and if approved they should provide useful alternatives for reaching LDL-C goals but the problem of long-term adherence to therapy will remain.