Consensus document on diagnosis and management of homozygous familial hypercholesterolaemia

A new position paper on the detection and clinical management of homozygous familial hypercholesterolaemia (HoFH) has been written by the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS). The recommendations are aimed at a wide spectrum of clinicians, including primary care physicians, paediatricians, dermatologists and endocrinologists, who may be the first to identify patients with suspected HoFH.

People with HoFH have markedly elevated circulating levels of LDL-c, and show accelerated, premature atherosclerotic cardiovascular disease (ACVD). Therefore, patients with this rare condition are at very high risk of CV disease and mortality. Unfortunately, HoFH is often diagnosed when considerable coronary atherosclerosis has already developed, thus there is a need for optimisation of treatment already in childhood. This position paper therefore underscores the importance of early identification of HoFH patients, and prompt referral to specialised centres and early initiation of appropriate treatment.

New insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, prompted the EAS Consensus Panel on Familial Hypercholesterolaemia to review the currently available data with the aim of providing clinical guidance for the recognition and management of HoFH.

The document discusses the epidemiology, currently known genetic factors, and metabolic characteristics of HoFH. Genetic and clinical diagnostic criteria for HoFH are outlined, including the presence of cutaneous or tuberous xanthomas in children, which are often the key driver of referral and HoFH diagnosis.
CV complications and the natural history of HoFH are described, along with recommendations on how to screen for and monitor subclinical atherosclerosis. Management should focus on lifestyle interventions, together with maximal statin therapy, often in combination with ezetimibe and other lipid-modifying therapy.
Emphasis is put on early initiation of lipid-lowering therapy, in order to reduce the burden of elevated LDL-c levels. Since guideline-recommended LDL-c target levels are often ambitious, lipoprotein apheresis is an important adjunctive treatment for HoFH. Clinical evidence suggests that lipoprotein apheresis can contribute to plaque regression and/or stabilisation and improve prognosis, and that it is cost-effective specifically in severe phenotypes.
New therapeutic approaches to lower LDL-c production, such as lomitapide (approved by FDA and EMA) and mipomersen (approved by FDA) are discussed. Novel agents that are currently in developed are also briefly touched on.

All recommendations of the consensus panel are briefly summarised in a box, for easy reference.

Cuchel M, Bruckert E, Ginsberg HN, et al., for the European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. July 22 2014. doi:10.1093/eurheartj/ehu274