New prospects for PCSK9 inhibition?

New prospects for PCSK9 inhibition? This commentary refers to ‘2017 update of ESC/EAS task force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia’, by U Landmesser et al., 2018;39:1131–1143. In 2017, this Task Force updated practical guidance for clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition following publication of FOURIER.1 Beyond licenced indications, PCSK9 inhibitors may have application in other high-risk conditions, such as severe hyperlipidaemia with liver failure,2 supported by pharmacodynamic data,3 although the lack of trials to date does not allow recommendations. Recent insights from FOURIER help to define patients at highest risk with elevated low-density lipoprotein cholesterol (LDL-C) levels who benefit most from PCSK9 inhibition. These include those with symptomatic peripheral artery disease (PAD), a group often under-recognized and undertreated, in whom evolocumab reduced major adverse cardiovascular events (MACE) by 27% and major adverse limb events by 37%, with benefits extending to LDL-C levels <0.26 mmol/L.4 Patients with recent or recurrent myocardial infarction (MI), or multivessel disease, at 34–90% higher risk of a MACE, also derived greater benefit from evolocumab than those without these characteristics (Sabatine MS, Annual Scientific Sessions, American Heart Association, 13 November 2017). Thus, irrespective of other vascular disease, symptomatic PAD, the timing and frequency of MI, or multivessel disease, associated with residual LDL-C burden, indicate very high-risk patients who merit consideration of PCSK9 inhibition. Will results from ODYSSEY OUTCOMES extend use of PCSK9 inhibitors to early post-MI patients? Such findings would align with the MIRACL trial5 and may imply further stabilization of atherosclerotic plaque from LDL-C lowering with PCSK9 inhibition. Conflict of interest: Potential conflicts of interest of the authors are denoted in reference 1. References 1 Landmesser U , Chapman MJ , Stock JK , Amarenco P , Belch JJF , Borén J , Farnier M , Ference BA , Gielen S , Graham I , Grobbee DE , Hovingh GK , Lüscher TF , Piepoli MF , Ray KK , Stroes ES , Wiklund O , Windecker S , Zamorano JL , Pinto F , Tokgözoglu L , Bax JJ , Catapano AL. 2017 update of ESC/EAS task force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia . Eur Heart J 2018 ; 39 : 1131 – 1143 . Google Scholar CrossRef Search ADS PubMed 2 Glowczynska R , Hus A , Raszeja-Wyszomirska J , Opolski G. Are the proprotein convertase subtilisin/kexin type 9 inhibitors new therapeutic chance for patients with familial hypercholesterolaemia and liver failure? Eur Heart J 2018 ; doi: 10.1093/eurheartj/ehy361. 3 Gibbs JP , Slatter JG , Egbuna O , Geller M , Hamilton L , Dias CS , Xu RY , Johnson J , Wasserman SM , Emery MG. Evaluation of evolocumab (AMG 145), a fully human anti-PCSK9 IgG2 monoclonal antibody, in subjects with hepatic impairment . J Clin Pharmacol 2017 ; 57 : 513 – 523 . Google Scholar CrossRef Search ADS PubMed 4 Bonaca MP , Nault P , Giugliano RP , Keech AC , Pineda AL , Kanevsky E , Kuder J , Murphy SA , Jukema JW , Lewis BS , Tokgozoglu L , Somaratne R , Sever PS , Pedersen TR , Sabatine MS. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) . Circulation 2018 ; 137 : 338 – 350 . Google Scholar CrossRef Search ADS PubMed 5 Schwartz GG , Olsson AG , Ezekowitz MD , Ganz P , Oliver MF , Waters D , Zeiher A , Chaitman BR , Leslie S , Stern T. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial . Jama 2001 ; 285 : 1711 – 1718 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

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Publisher
Oxford University Press
Copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
ISSN
0195-668X
eISSN
1522-9645
D.O.I.
10.1093/eurheartj/ehy147
Publisher site
See Article on Publisher Site

Abstract

This commentary refers to ‘2017 update of ESC/EAS task force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia’, by U Landmesser et al., 2018;39:1131–1143. In 2017, this Task Force updated practical guidance for clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition following publication of FOURIER.1 Beyond licenced indications, PCSK9 inhibitors may have application in other high-risk conditions, such as severe hyperlipidaemia with liver failure,2 supported by pharmacodynamic data,3 although the lack of trials to date does not allow recommendations. Recent insights from FOURIER help to define patients at highest risk with elevated low-density lipoprotein cholesterol (LDL-C) levels who benefit most from PCSK9 inhibition. These include those with symptomatic peripheral artery disease (PAD), a group often under-recognized and undertreated, in whom evolocumab reduced major adverse cardiovascular events (MACE) by 27% and major adverse limb events by 37%, with benefits extending to LDL-C levels <0.26 mmol/L.4 Patients with recent or recurrent myocardial infarction (MI), or multivessel disease, at 34–90% higher risk of a MACE, also derived greater benefit from evolocumab than those without these characteristics (Sabatine MS, Annual Scientific Sessions, American Heart Association, 13 November 2017). Thus, irrespective of other vascular disease, symptomatic PAD, the timing and frequency of MI, or multivessel disease, associated with residual LDL-C burden, indicate very high-risk patients who merit consideration of PCSK9 inhibition. Will results from ODYSSEY OUTCOMES extend use of PCSK9 inhibitors to early post-MI patients? Such findings would align with the MIRACL trial5 and may imply further stabilization of atherosclerotic plaque from LDL-C lowering with PCSK9 inhibition. Conflict of interest: Potential conflicts of interest of the authors are denoted in reference 1. References 1 Landmesser U , Chapman MJ , Stock JK , Amarenco P , Belch JJF , Borén J , Farnier M , Ference BA , Gielen S , Graham I , Grobbee DE , Hovingh GK , Lüscher TF , Piepoli MF , Ray KK , Stroes ES , Wiklund O , Windecker S , Zamorano JL , Pinto F , Tokgözoglu L , Bax JJ , Catapano AL. 2017 update of ESC/EAS task force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia . Eur Heart J 2018 ; 39 : 1131 – 1143 . Google Scholar CrossRef Search ADS PubMed 2 Glowczynska R , Hus A , Raszeja-Wyszomirska J , Opolski G. Are the proprotein convertase subtilisin/kexin type 9 inhibitors new therapeutic chance for patients with familial hypercholesterolaemia and liver failure? Eur Heart J 2018 ; doi: 10.1093/eurheartj/ehy361. 3 Gibbs JP , Slatter JG , Egbuna O , Geller M , Hamilton L , Dias CS , Xu RY , Johnson J , Wasserman SM , Emery MG. Evaluation of evolocumab (AMG 145), a fully human anti-PCSK9 IgG2 monoclonal antibody, in subjects with hepatic impairment . J Clin Pharmacol 2017 ; 57 : 513 – 523 . Google Scholar CrossRef Search ADS PubMed 4 Bonaca MP , Nault P , Giugliano RP , Keech AC , Pineda AL , Kanevsky E , Kuder J , Murphy SA , Jukema JW , Lewis BS , Tokgozoglu L , Somaratne R , Sever PS , Pedersen TR , Sabatine MS. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) . Circulation 2018 ; 137 : 338 – 350 . Google Scholar CrossRef Search ADS PubMed 5 Schwartz GG , Olsson AG , Ezekowitz MD , Ganz P , Oliver MF , Waters D , Zeiher A , Chaitman BR , Leslie S , Stern T. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial . Jama 2001 ; 285 : 1711 – 1718 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Heart JournalOxford University Press

Published: Mar 22, 2018

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