PCSK9 inhibitors and cardiovascular disease: heralding a new therapeutic era

被引:48
作者
Chapman, M. John [1 ]
Stock, Jane K. [2 ]
Ginsberg, Henry N. [3 ]
机构
[1] Pitie Salpetriere Univ Hosp, Natl Inst Hlth & Med Res, INSERM, 83 Blvd Hop, F-75651 Paris 13, France
[2] Minerva Mill Innovat Ctr, PCSK9 Forum Secretariat, Alcester, England
[3] Columbia Univ, Coll Phys & Surg, Irving Inst, Dept Med, New York, NY USA
关键词
alirocumab; cardiovascular risk; evolocumab; low-density lipoprotein cholesterol; proprotein convertase subtilisin; kexin type 9 inhibitors; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; DENSITY-LIPOPROTEIN RECEPTOR; SUBTILISIN/KEXIN TYPE 9; EVOLOCUMAB AMG 145; PLACEBO-CONTROLLED TRIAL; EUROPEAN ATHEROSCLEROSIS SOCIETY; CORONARY-HEART-DISEASE; ODYSSEY OPTIONS I; MONOCLONAL-ANTIBODY; STATIN THERAPY;
D O I
10.1097/MOL.0000000000000239
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Purpose of reviewThe first monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have been approved for clinical use. This timely review highlights recent developments.Recent findingsLow-density lipoprotein cholesterol (LDL-C) is the primary driver of atherosclerosis and the key target for intervention. Yet despite best treatment including statins, attaining sufficient LDL-C lowering can be problematic for high cardiovascular risk patients. The development of PCSK9 inhibitors, driven by novel genetic and mechanistic insights, offers an answer. Removal of circulating PCSK9 increases LDL receptor availability, and thus markedly decreases plasma LDL-C levels (by approximate to 50-60%), and is additive to the lipid lowering effects of statins and ezetimibe. PCSK9 inhibition also reduces (by 25-30%) plasma levels of lipoprotein(a), a causal factor in atherosclerotic vascular disease, suggestive of partial catabolism of lipoprotein(a) by LDL receptors. The ODYSSEY and PROFICIO (Programme to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different Populations) clinical trial programmes involving a wide range of high-risk patients, including statin intolerant patients, have confirmed the consistency of the LDL response, even with concomitant high-intensity statin or nonstatin therapy. Extensive evidence to date attests to a favourable safety and tolerability profile for these innovative agents.SummaryThe new pharmacotherapeutic era of PCSK9 inhibition is upon us, promising major reduction in cardiovascular events across a wide spectrum of high-risk patients.
引用
收藏
页码:511 / 520
页数:10
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