The Knowns and Unknowns of Contemporary Statin Therapy for Familial Hypercholesterolemia

Abstract

Purpose of Review Statins are first-line therapy for lowering low-density lipoprotein (LDL) cholesterol in familial hypercholesterolemia (FH), particularly in heterozygous patients. We review advances and new questions on the use of statins in FH. Recent Findings Cumulative evidence from registry data and sub-analyses of clinical trials mandates the value of statin therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in FH. Statins are safe in children and adolescents with FH, with longer term cardiovascular benefits. The potentially toxic effects of statins in pregnancy need to be considered, but no association has been reported in prospective cohort studies with birth defects. There is no rationale for discontinuation of statins in elderly FH unless indicated by adverse events. FH is undertreated, with > 80% of statin-treated FH patients failing to attain LDL cholesterol treatment targets. This may relate to adherence, tolerability, and genetic differences in statin responsiveness. Statin treatment from childhood may reduce the need for stringent cholesterol targets. Combination of statins with ezetimibe and PCSK9 inhibitors significantly improves the efficacy of treatment. Whether statin use could improve the clinical course of FH patients with COVID-19 and other respiratory infections remains an unsolved issue for future research. Summary Statins are the mainstay for primary and secondary prevention of ASCVD in FH. Sustained long-term optimal statin treatment from an early age can effectively prevent ASCVD over decades of life. Despite their widespread use, statins merit further investigation in FH.

Implications of new clinical practice guidance on familial hypercholesterolaemia for Australian general practitioners

“…3 The importance of early diagnosis and treatment of FH in girls should never be underestimated. 31 Pregnancy and lactation can result in the loss of effective years of statin treatment due to childbearing. 31 Adherence to statin treatment can be difficult, especially in young people.…”

“…31 Pregnancy and lactation can result in the loss of effective years of statin treatment due to childbearing. 31 Adherence to statin treatment can be difficult, especially in young people. The need for early and ongoing treatment at optimal doses should be stressed to improve future ASCVD outcomes.…”

“…The need for early and ongoing treatment at optimal doses should be stressed to improve future ASCVD outcomes. 31 The cost-effectiveness of such an approach is increasingly recognised. 32…”

Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence

“…They are effective hypolipidemic drugs that act by inhibiting the production of mevalonate in the biosynthetic pathway of cholesterol. Multicenter clinical trials have demonstrated that these compounds are effective in reducing cardiovascular events and increase the rate of survival in patients [ 2 ]. Thus, statins represent the first line therapy in the prevention and treatment of metabolic syndrome [ 3 ] and cardiovascular diseases (CVD), that are the primary causes of mortality in the world.…”

Cardiovascular events in patients with familial hypercholesterolemia and hyperlipoproteinaemia (a): Indications for lipoprotein apheresis in Poland

“…Intensive lipid‐lowering therapies have been proven to reduce cardiovascular (CV) risk. Nevertheless, individuals who present the most severe phenotype of FH due to extremely high baseline, low‐density lipoprotein cholesterol (LDL‐C) levels do not reach therapeutic targets even with the maximal doses of available pharmacotherapy 6‐10 . Currently, there are also no commercially available medications or lifestyle modifications for hyper‐Lp(a) that are capable of efficiently reducing lipoprotein (a) [Lp(a)] levels along with CV event rate attenuation.…”