Old challenges and new opportunities in the clinical management of heterozygous familial hypercholesterolemia (HeFH): The promises of PCSK9 inhibitors

被引:9
作者
Arca, Marcello [1 ]
机构
[1] Sapienza Univ Rome, Dept Internal Med & Allied Sci, Atherosclerosis Unit, Rome, Italy
关键词
Heterozygous familial hypercholesterolemia; Low-density lipoprotein cholesterol; Cardiovascular risk; PCSK9; inhibitors; Alirocumab; Evolocumab; DENSITY-LIPOPROTEIN RECEPTOR; ASSOCIATION EXPERT PANEL; CORONARY-ARTERY-DISEASE; SUBTILISIN/KEXIN TYPE 9; CHOLESTEROL-LOWERING TREATMENT; MONOCLONAL-ANTIBODY; POSTTRANSCRIPTIONAL REGULATION; GENERAL-POPULATION; FRENCH-CANADIANS; NATURAL-HISTORY;
D O I
10.1016/j.atherosclerosis.2016.09.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Heterozygous familial hypercholesterolemia (HeFH) is a common (early estimates suggested a prevalence of 1 in 500 individuals, but recent studies have indicated that it may be higher) genetic disorder characterized by markedly elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C). HeFH is associated with an elevated risk of premature coronary heart disease, stroke, and peripheral vascular disease. Despite the availability of reliable diagnostic criteria (high LDL-C levels, family history or premature CHD and hypercholesterolemia, cerebral/peripheral vascular disease, and the presence of tendon xanthomata or presence of arcus cornealis before age of 45), HeFH is underdiagnosed and undertreated worldwide. Moreover, while there are effective treatments available to decrease LDL-C and prevent early-onset heart disease in individuals with HeFH, because of the high baseline levels of LDL-C, the achievement of target LDL-C levels remains a challenge. In recent years, a number of novel therapies to lower LDL-C levels in HeFH have been developed, including the monoclonal antibodies against serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9), alirocumab and evolocumab, which have the potential to reduce LDL-C by an additional 50%-60% when prescribed in combination with standard lipid-lowering drugs. This review summarizes the challenges in clinical management of subjects with HeFH, with a focus on emerging treatments, and highlights the status of HeFH diagnosis and treatment in Italy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:134 / 145
页数:12
相关论文
共 101 条
[61]   Extent of underdiagnosis of familial hypercholesterolaemia in routine practice: prospective registry study [J].
Neil, HAW ;
Hammond, T ;
Huxley, R ;
Matthews, DR ;
Humphries, SE .
BRITISH MEDICAL JOURNAL, 2000, 321 (7254) :148-148
[62]   Probabilistic cost-effectiveness analysis of cascade screening for familial hypercholesterolaemia using alternative diagnostic and identification strategies [J].
Nherera, L. ;
Marks, D. ;
Minhas, R. ;
Thorogood, M. ;
Humphries, S. E. .
HEART, 2011, 97 (14) :1175-1181
[63]   Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease [J].
Nordestgaard, Borge G. ;
Chapman, M. John ;
Humphries, Steve E. ;
Ginsberg, Henry N. ;
Masana, Luis ;
Descamps, Olivier S. ;
Wiklund, Olov ;
Hegele, Robert A. ;
Raal, Frederick J. ;
Defesche, Joep C. ;
Wiegman, Albert ;
Santos, Raul D. ;
Watts, Gerald F. ;
Parhofer, Klaus G. ;
Hovingh, G. Kees ;
Kovanen, Petri T. ;
Boileau, Catherine ;
Averna, Maurizio ;
Boren, Jan ;
Bruckert, Eric ;
Catapano, Alberico L. ;
Kuivenhoven, Jan Albert ;
Pajukanta, Paeivi ;
Ray, Kausik ;
Stalenhoef, Anton F. H. ;
Stroes, Erik ;
Taskinen, Marja-Riitta ;
Tybjaerg-Hansen, Anne .
EUROPEAN HEART JOURNAL, 2013, 34 (45) :3478-+
[64]   Frequency of familial hypercholesterolemia in patients with early-onset coronary artery disease admitted to a coronary care unit [J].
Pang, Jing ;
Poulter, Elissa B. ;
Bell, Damon A. ;
Bates, Timothy R. ;
Jefferson, Vicki-Lee ;
Hillis, Graham S. ;
Schultz, Carl J. ;
Watts, Gerald F. .
JOURNAL OF CLINICAL LIPIDOLOGY, 2015, 9 (05) :703-708
[65]   Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver [J].
Park, SW ;
Moon, YA ;
Horton, JD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (48) :50630-50638
[66]   Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies [J].
Patel, Roshni S. ;
Scopelliti, Emily M. ;
Savelloni, Julie .
PHARMACOTHERAPY, 2015, 35 (12) :1189-1203
[67]   Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: A large cross-sectional study in The Netherlands [J].
Pijlman, A. H. ;
Huijgen, R. ;
Verhagen, S. N. ;
Imholz, B. P. M. ;
Liem, A. H. ;
Kastelein, J. J. P. ;
Abbink, E. J. ;
Stalenhoef, A. F. H. ;
Visseren, F. L. J. .
ATHEROSCLEROSIS, 2010, 209 (01) :189-194
[68]   Low-Density Lipoprotein Cholesterol-Lowering Effects of AMG 145, a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia The Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) Randomized Trial [J].
Raal, Frederick ;
Scott, Rob ;
Somaratne, Ransi ;
Bridges, Ian ;
Li, Gang ;
Wasserman, Scott M. ;
Stein, Evan A. .
CIRCULATION, 2012, 126 (20) :2408-2417
[69]   PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial [J].
Raal, Frederick J. ;
Stein, Evan A. ;
Dufour, Robert ;
Turner, Traci ;
Civeira, Fernando ;
Burgess, Lesley ;
Langslet, Gisle ;
Scott, Russell ;
Olsson, Anders G. ;
Sullivan, David ;
Hovingh, G. Kees ;
Cariou, Bertrand ;
Gouni-Berthold, Ioanna ;
Somaratne, Ransi ;
Bridges, Ian ;
Scott, Rob ;
Wasserman, Scott M. ;
Gaudet, Daniel .
LANCET, 2015, 385 (9965) :331-340
[70]   Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial [J].
Raal, Frederick J. ;
Honarpour, Narimon ;
Blom, Dirk J. ;
Hovingh, G. Kees ;
Xu, Feng ;
Scott, Rob ;
Wasserman, Scott M. ;
Stein, Evan A. ;
Investigators, T. E. S. L. A. .
LANCET, 2015, 385 (9965) :341-350