Replacing statins with PCSK9-inhibitors and delaying treatment until 18 years of age in patients with familial hypercholesterolaemia is not a good idea

Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new, powerful, and very promising therapeutic option for reducing low-density lipoprotein (LDL)-cholesterol (LDL-C).1 Alirocumab and evolocumab are fully human monoclonal antibodies (mAbs) against PCSK9. The drugs have just been marketed and are in the process of being adopted in the treatment of high-risk patients, mainly as add-on to conventional lipid-lowering therapy or in those who cannot tolerate an effective dose of statins. In this issue of the European Heart Journal , Vuorio et al. 2 present an idea for a new therapeutic option in treating young patients with familial hypercholesterolaemia (FH), i.e. delay of treatment until 18 years of age and then initiating lifelong PCSK9-inhibiting treatment. The reasoning being that the lifelong LDL-C burden will be considerably lower compared with initiating low-dose statin therapy at age 10 years and high-dose statin from age 18 years. For a number of reasons, outlined below, I disagree with this idea. The approval of alirocumab and evolocumab is based on results from randomized trials involving <4000 persons for each drug.3,4 Almost all patients in the trials, including the FH patients, were middle-aged5 and almost all FH-patients received PCSK9 mAbs in addition to maximally tolerated statin ± ezetimibe, i.e. not in monotherapy.6,7 Apart from two post hoc analyses of cardiovascular (CV) events,8,9 no results from CV endpoint trials are yet available, although the first results from such trials are expected …