Systematic Review of Low‐Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia

Abstract

BackgroundApheresis is an important treatment for reducing low‐density lipoprotein cholesterol (LDL‐C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL‐C apheresis for FH.Methods and ResultsElectronic databases were searched for publications of LDL‐C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000–2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL‐C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty‐eight studies met the inclusion criteria: 8 open‐label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL‐C apheresis as first‐line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL‐C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL‐C reduction after apheresis: 57–75% for patients with homozygous FH and 58–63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment.Conclusions LDL‐C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL‐C to target levels. While apheresis reduces LDL‐C, high per‐session costs and the frequency of guideline‐recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH.

Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care

“…A small population of LLT‐intolerant patients with elevated LDL‐C levels may be eligible for apheresis. This procedure is widely used in Germany, but less so in other European countries and the USA . Anti‐PCSK9 antibodies could replace apheresis in some patients: 48‐week treatment with evolocumab (420 mg every 2 weeks) in 34 patients with HoFH resulted in 21% reduction in mean LDL‐C and 15% of patients stopping or reducing the frequency of apheresis .…”

Homozygous familial hypercholesterolemia with stenosis of the left anterior descending coronary artery successfully treated with weekly low‐density lipoprotein apheresis for 16 years without percutaneous coronary intervention

“…According to the most recent observational study, over 90% of individuals with FH are not appropriately diagnosed . Treatments for HoFH include a maximal dose of a strong statin such as atorvastatin, ezetimibe, bile acid‐binding resins, and LDL apheresis and/or proprotein convertase subtilisin‐kexin type 9 inhibitors . In Japan, the maximum doses of atorvastatin, rosuvastatin, and pitavastatin are 40, 20, and 4 mg/d, respectively, even for cases of familial hypercholesterolemia, whereas in the United States and Europe, the maximum dose of atorvastatin is 80 mg/d.…”

“…Familial hypercholesterolemia (FH) is an autosomal disorder of lipid metabolism characterized by remarkably elevated low‐density lipoprotein cholesterol (LDL‐C) levels, cutaneous xanthomas, and a family history of premature atherosclerosis. Prevalence of homozygous (HoFH) and heterozygous FH is 1:160 000 and 1:250, respectively . The cholesterol exposure burden in HoFH greatly increases the risk of atherosclerotic cardiovascular disease and premature death.…”

Therapeutic strategies for atherosclerosis and atherothrombosis: Past, present and future

“…However, this drug is only approved for treating homozygous hypercholesterolemia by the FDA, but not in European due to safety concerns related to hepatotoxicity and increased cardiovascular risk (16). Currently, LDL apheresis is widely accepted as firstline therapy for homozygous familial hypercholesterolaemia (34).…”