Additional drug therapy to meet LDL-C targets

If the LDL-C target is not achieved with the maximum tolerated dose of a statin, consider adding ezetimibe. A randomised controlled trial in patients with established ASCVD demonstrated improved cardiovascular outcomes in patients treated with ezetimibe plus statin therapy¹ Cannon, 2015. The effect of ezetimibe on cardiovascular outcomes in the primary prevention of ASCVD has not been studied, although some evidence suggests a reduced risk of coronary artery disease with ezetimibeMyocardial Infarction Genetics Consortium Investigators, 2014.

If the LDL-C target is not achieved with the combination of the maximum tolerated dose of a statin plus ezetimibe, consider adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor ². A randomised controlled trial in patients with established ASCVD demonstrated improved cardiovascular outcomes in patients treated with a PCSK9 inhibitor added to statin therapy³ Sabatine, 2017; do not add a PCSK9 inhibitor unless ezetimibe has been ineffective or not tolerated. The effect of PCSK9 inhibitors on cardiovascular outcomes in the primary prevention of ASCVD has not been studied; however, genetic studies of people with PCSK9 loss-of-function mutations have shown they have reduced LDL-C concentrations and a reduced risk of coronary artery disease⁴ ⁵ Cohen, 2006 Ference, 2016.

Inclisiran is a small interfering RNA therapy that reduces LDL-C by reducing production of PCSK9 in the liverRay 2023. At the time of writing, the impact of inclisiran on primary or secondary prevention of atherosclerotic cardiovascular events has not been studied. It can be considered as an alternative to a PCSK9 inhibitor in patients who have not achieved the recommended LDL-C target with the maximum tolerated dose of a statin plus ezetimibe⁶.

¹ Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372(25):2387-97. URL Return

² At the time of writing, the PCSK9 inhibitors evolocumab and alirocumab are subsidised on the PBS for hypercholesterolaemia under specific criteria. See the PBS website for current information.Return

³ Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376(18):1713-22. URL Return

⁴ Cohen JC, Boerwinkle E, Mosley TH, Jr., Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354(12):1264-72. URL Return

⁵ Ference BA, Robinson JG, Brook RD, Catapano AL, Chapman MJ, Neff DR, et al. Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med 2016;375(22):2144-53. URL Return

⁶ At the time of writing, inclisiran is subsidised on the Pharmaceutical Benefits Scheme (PBS) for hypercholesterolaemia under specific criteria. See the PBS website for current information.Return