In 2016, the National Lipid Association conducted an online survey on PCSK9 inhibitor use and barriers to prescription among experienced healthcare workers who provide care to high-risk patients with ASCVD or familial hypercholesterolemia (FH).
A comprehensive literature search regarding lipoprotein apheresis in patients with familial hypercholesterolaemia and its combination with PCSK9 inhibitors has been performed.
In good agreement with previous studies in patients with familial hypercholesterolaemia, our study in the Japanese general population showed that rare variants in LDLR and PCSK9 were associated with the onset age of MI by altering LDL-cholesterol levels.
Nevertheless, rare clinical presentations in families with extreme phenotypes can sometimes identify novel pathways that can serve as therapeutic targets, such as the discovery of PCSK9 inhibitors for familial hypercholesterolemia or small molecular inhibitors of myosin ATPase activities for hypertrophic cardiomyopathy.
Mutations in the low-density lipoprotein (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin 9 (PCSK9), and LDLRAP1 genes have been associated with FH.
A separate meta-analysis of trials recruiting familial hypercholesterolemia patients has showed a tendency to harm for all outcomes with PCSK9 antibodies.
Definite FH includes: (1) elevated LDL-C (≥ 8.50 mmol/L); or (2) LDL-C ≥ 5.0 mmol/L (for age 40 years or older; ≥ 4.0 mmol/L if age younger than 18 years; and ≥ 4.5 mmol/L if age is between 18 and 39 years) when associated with at least 1 of: (1) tendon xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the proband or first-degree relative.
Lipoprotein apheresis and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are last therapeutic resorts in patients with familial hypercholesterolemia (FH).
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) are an innovative treatment option for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require further lowering of low-density lipoprotein cholesterol.
PCSK9 inhibitor plus statin did not show good cost-effectiveness for triple-vessel CAD; however, it showed good cost-effectiveness for patients with triple-vessel CAD and poorly controlled FH in Japan.
Among the 3381 index cases included with these characteristics in the French registry for familial hypercholesterolemia, 2054 underwent molecular diagnosis and 1150 (56%) were found to have mutations (93.5% in LDL Receptor (LDLR), 4.7% in apolipoprotein B and 1.8% in Proprotein convertase subtilisin/kexin type 9).
Autosomal dominant hypercholesterolemia, being referred to as familial hypercholesterolemia (FH), is mainly due to defective LDL receptor (LDLR) function, but is also associated with variants in genes encoding APOB (LDLR ligand) and PCSK9, the catabolic regulator of LDLR.
Recently the fully human monoclonal antibodies against proprotein convertase subtilisin/kexin 9 (PCSK9), alirocumab (Praluent®) and evolocumab (Repatha®), which have been shown to decrease LDL-C by up to 70% have been approved in Europe for use in patients with primary hypercholesterolemia not at LDL-C target while on maximally tolerated lipid-lowering therapy and specifically for patients with statin intolerance and in the USA for patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia requiring additional LDL-C lowering.
Moreover, PCSK9 inhibitors have been approved for patients with either familial hypercholesterolemia or atherosclerotic cardiovascular disease, who require additional reduction of LDL-C.
This study was aimed at screening the LDLR, APOB and PCSK9 genes in Hypercholesterolemic patients to define the genetic spectrum of FH in Indian population.
Despite the use of high-dose statins and the recent addition of proprotein convertase subtilisin/kexin type 9 inhibitors as a treatment option, many patients with homozygous FH fail to achieve optimal reductions of LDL-c levels.
The aim of this study is to investigate the relation between lipoprotein(a) [Lp(a)] and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations, and their complex, in patients with potential familial hypercholesterolemia (FH), depending on apo(a) phenotype.
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce low-density lipoprotein cholesterol (LDL-C) levels and are approved for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional LDL-C lowering.