Homozygous familial hypercholesterolaemia ( HoFH ) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol ( LDL-C ) and accelerated, premature atherosclerotic cardiovascular disease ( ACVD ). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of homozygous familial hypercholesterolaemia, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society ( EAS ) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of homozygous familial hypercholesterolaemia.
Early diagnosis of homozygous familial hypercholesterolaemia and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous familial hypercholesterolaemia in both parents, are suggestive of homozygous familial hypercholesterolaemia.
Consensus Panel recommends that patients with suspected homozygous familial hypercholesterolaemia are promptly referred to specialist centres for a comprehensive atherosclerotic cardiovascular disease evaluation and clinical management.
Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with Ezetimibe ( Ezetrol, Zetia ) and other lipid-modifying therapy.
As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years.
The number of therapeutic approaches has increased following approval of Lomitapide ( Juxtapid in Unites States ; Lojuxta in European Union ) and Mipomersen ( Kynamro ) for homozygous familial hypercholesterolaemia.
Given the severity of atherosclerotic cardiovascular disease, Consensus Panel recommends regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.
In conclusion, the EAS Consensus Panel highlights the need for early identification of homozygous familial hypercholesterolaemia patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected homozygous familial hypercholesterolaemia. ( Xagena )
Cuchel M et al, Eur Heart J 2014;35:2146-2157