Statin alternatives for the treatment of hypercholesterolemia - a safety evaluation.

Introduction: Statins are well established as the first-line treatment to reduce low-density-lipoprotein cholesterol (LDL-C) and cardiovascular (CV) events, but some patients are unable to tolerate effective doses or sometimes any dose of statins and alternative treatments may be required.

Areas covered: In this review we summarize the relevant published literature obtained from a PubMed search on the safety of statin alternatives for the treatment of hypercholesterolemia.

Expert opinion: The main alternatives to statins are ezetimibe, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab, alirocumab, and inclisiran, and the recently approved bempedoic acid. These have all shown an excellent safety profile and have not been associated with skeletal muscle symptoms or with increased risk of new onset diabetes and they have no major drug interactions. The injectable PCSK9 inhibitors are associated with a small increase in injection site reactions which are usually of mild or moderate intensity. Bempedoic acid is associated with a small increase in plasma uric acid and slightly increased frequency of episodes of gout in susceptible subjects. The cost and availability and the degree of lowering of LDL-C required are more likely to determine the choice of statin alternatives than the safety issues.