High-dose potent
statin therapy in combination with
ezetimibe is now standard practice for the treatment of adult patients with heterozygous
familial hypercholesterolemia (heFH), as the result of numerous studies in patients with primary
hypercholesterolemia or heFH. These studies have shown the combination to be both effective and safe in the short to medium term. Recently, short-term
ezetimibe therapy has also been shown to be effective and safe in combination with
statin therapy for children and adolescents with heFH. Effective
statin-
ezetimibe combination
therapy is capable of achieving near-normal
lipid profiles in heFH patients, with expected improvement in risk for
cardiovascular disease (CVD) and improved life expectancy resulting predominantly from reduction in levels of
low-density lipoprotein cholesterol. There are few data to support a pleiotropic action of
ezetimibe with regard to CVD benefit, unlike
therapy with
statins. No serious and unexpected clinical adverse effects of combination
statin-
ezetimibe therapy have emerged till date, although data are limited in children and adolescents, for whom longer-term studies are required. Recent data suggesting possible proatherogenic effects of
ezetimibe require confirmation. One large long-term randomized controlled clinical outcomes trial is in progress in non-FH patients to determine the efficacy and safety of
ezetimibe therapy; it is unlikely that such a trial will ever be performed in patients with FH.