Poststatin Lipid Therapeutics: A Review

Xiaoming Jia; Patrick Lorenz; Christie M. Ballantyne

doi:10.14797/mdcj-15-1-32

Poststatin Lipid Therapeutics: A Review

Methodist DeBakey Cardiovascular Journal

Volume 15 (2019): Issue 1

By: Xiaoming Jia, Patrick Lorenz and Christie M. Ballantyne

Open Access

|Jan 2019

Abstract

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins remain the first-line therapy for patients with elevated LDL-C and increased risk. However, many at-risk patients do not achieve adequate LDL-C lowering with statin monotherapy or do not tolerate statins because of side effects. Recent cardiovascular outcome trials involving ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated efficacy of nonstatin therapies in further reducing LDL-C levels and ASCVD risk. This review highlights the available nonstatin therapeutic options and explores important novel therapeutic approaches currently under development.

References

Benjamin EJ Virani SS Callaway CW .; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association Circulation 2018 Mar 20 137 12 e67 e492
Search in Google Scholar Back to article
Weir HK Anderson RN Coleman King SM Heart Disease and Cancer Deaths - Trends and Projections in the United States, 1969–2020 Prev Chronic Dis 2016 Nov 17 13 E157
Search in Google Scholar Back to article
Baigent C Blackwell L Emberson J .; Cholesterol Treatment Trialists' (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials Lancet 2010 Nov 13 376 9753 1670 81
Search in Google Scholar Back to article
Stroes ES Thompson PD Corsini A Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management Eur Heart J 2015 May 1 36 17 1012 22
Search in Google Scholar Back to article
Phan BA Dayspring TD Toth PP Ezetimibe therapy: mechanism of action and clinical update Vasc Health Risk Manag 2012 8 415 27
Search in Google Scholar Back to article
Pandor A Ara RM Tumur I Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials J Intern Med 2009 May 265 5 568 80
Search in Google Scholar Back to article
Morrone D Weintraub WS Toth PP Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials Atherosclerosis 2012 Aug 223 2 251 61
Search in Google Scholar Back to article
Rossebø AB Pedersen TR Boman K .; SEAS Investigators Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis N Engl J Med 2008 Sep 25 359 13 1343 56
Search in Google Scholar Back to article
Baigent C Landray MJ Reith C .; SHARP Investigators The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial Lancet 2011 Jun 25 377 9784 2181 92
Search in Google Scholar Back to article
Cannon CP Blazing MA Giugliano RP .; IMPROVE-IT Investigators Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes N Engl J Med 2015 Jun 18 372 25 2387 97
Search in Google Scholar Back to article
Bohula EA Morrow DA Giugliano RP Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention J Am Coll Cardiol 2017 Feb 28 69 8 911 21
Search in Google Scholar Back to article
Lloyd-Jones DM Morris PB Ballantyne CM 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways J Am Coll Cardiol 2017 Oct 3 70 14 1785 822
Search in Google Scholar Back to article
Goldstein JL Brown MS Anderson RG Russell DW Schneider WJ Receptor-mediated endocytosis: concepts emerging from the LDL receptor system Annu Rev Cell Biol 1985 1 1 39
Search in Google Scholar Back to article
Tavori H Fan D Blakemore JL Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation Circulation 2013 Jun 18 127 24 2403 13
Search in Google Scholar Back to article
Sabatine MS Giugliano RP Keech AC .; FOURIER Steering Committee and Investigators Evolocumab and clinical outcomes in patients with cardiovascular disease N Engl J Med 2017 May 4 376 18 1713 22
Search in Google Scholar Back to article
Schwartz GG Steg PG Szarek M .; ODYSSEY OUTCOMES Committees and Investigators Alirocumab and cardiovascular outcomes after acute coronary syndrome N Engl J Med. 2018 Nov 7
Search in Google Scholar Back to article
ICER [Internet] Boston, MA Institute for Clinical and Economic Review c2018 Evolocumab for treatment of high cholesterol: effectiveness and value—new evidence update; 2017 Sep 11 [accessed 2018 Sep 17]. Available from: https://icer-review.org/wp-content/uploads/2017/06/ICER_PCSK9_NEU_091117.pdf
Search in Google Scholar Back to article
ICER [Internet] Boston, MA Institute for Clinical and Economic Review c2018 Alirocumab for treatment of high cholesterol: effectiveness and value—preliminary new evidence update; 2018 Mar 10 [Accessed 2018 Sep 17]. Available from: https://icer-review.org/wp-content/uploads/2018/03/Alirocumab-Preliminary-New-Evidence-Update_03102018.pdf
Search in Google Scholar Back to article
Akdim F Stroes ES Sijbrands EJ Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy J Am Coll Cardiol 2010 Apr 13 55 15 1611 8
Search in Google Scholar Back to article
Carthew RW Sontheimer EJ Origins and mechanisms of miRNAs and siRNAs Cell 2009 Feb 20 136 4 642 55
Search in Google Scholar Back to article
Ray KK Landmesser U Leiter LA Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol N Engl J Med 2017 Apr 13 376 15 1430 40
Search in Google Scholar Back to article
Clinical Trials [Internet] Bethesda, MD U.S. National Library of Medicine c2018 Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) (ORION-9); 2018 Apr 9 [cited 2018 Oct 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03397121
Search in Google Scholar Back to article
Clinical Trials [Internet] Bethesda, MD U.S. National Library of Medicine c2018 Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol (ORION-10); 2018 Apr 23 [cited 2018 Oct 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03399370
Search in Google Scholar Back to article
Clinical Trials [Internet] Bethesda, MD U.S. National Library of Medicine c2018 Inclisiran for Subjects With ACSVD or ACSVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol (ORION-11); 2018 Apr 26 [cited 2018 Oct 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03400800
Search in Google Scholar Back to article
TIMI Study Group [Internet] Boston, MA TIMI Study Group c2018 HPS-4/TIMI 65 ORION-4l; 2018 [Accessed 2018 Sep 17]. Available from: http://www.timi.org/index.php?page=orion-4
Search in Google Scholar Back to article
Bilen O Ballantyne CM Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase Curr Atheroscler Rep 2016 Oct 18 10 61
Search in Google Scholar Back to article
Penson P McGowan M Banach M Evaluating bempedoic acid for the treatment of hyperlipidaemia Expert Opin Investig Drugs 2017 Feb 26 2 251 9
Search in Google Scholar Back to article
Ballantyne CM Davidson MH Macdougall DE Efficacy and safety of a novel dual modulator of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase in patients with hypercholesterolemia: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial J Am Coll Cardiol 2013 Sep 24 62 13 1154 62
Search in Google Scholar Back to article
Gutierrez MJ Rosenberg NL Macdougall DE Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus Arterioscler Thromb Vasc Biol 2014 Mar 34 3 676 83
Search in Google Scholar Back to article
Ballantyne CM McKenney JM MacDougall DE Effect of ETC-1002 on Serum Low-Density Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy Am J Cardiol 2016 117 1928 33
Search in Google Scholar Back to article
Ballantyne CM Banach M Mancini GBJ Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study Atherosclerosis 2018 Jun 12
Search in Google Scholar Back to article
Clinical Trials [Internet] Bethesda, MD U.S. National Library of Medicine c2018 Evaluation of Major Cardiovascular Events in Patients With, or at High Risk for, Cardiovascular Disease Who Are Statin Intolerant Treated With Bempedoic Acid (ETC-1002) or Placebo (CLEAR Outcomes); 2016 Dec 15 [cited 2018 Oct 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03400800
Search in Google Scholar Back to article
Erqou S Kaptoge S Perry PL .; Emerging Risk Factors Collaboration Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality JAMA 2009 Jul 22 302 4 412 23
Search in Google Scholar Back to article
Willeit P Kiechl S Kronenberg F Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study J Am Coll Cardiol 2014 Sep 2 64 9 851 60
Search in Google Scholar Back to article
Banach M Lipoprotein (a)-We Know So Much Yet Still Have Much to Learn J Am Heart Assoc 2016 Apr 23 5 4 e003597
Search in Google Scholar Back to article
Koschinsky ML Boffa MB Marcovina SM Lipoprotein(a) In Ballantyne CM editor Clinical Lipidology: A Companion to Braunwald's Heart Disease Philadelphia, PA Elsevier Saunders 2015 p 109 27
Search in Google Scholar Back to article
Viney NJ Yeang C Yang X Xia S Witztum JL Tsimikas S Relationship between “LDL-C”, estimated true LDL-C, apolipoprotein B-100, and PCSK9 levels following lipoprotein(a) lowering with an antisense oligonucleotide J Clin Lipidol. 2018 May - Jun 12 3 702 10
Search in Google Scholar Back to article
Khera AV Everett BM Caulfield MP Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) Circulation 2014 Feb 11 129 6 635 42
Search in Google Scholar Back to article
Kotani K Banach M Lipoprotein(a) and inhibitors of proprotein convertase subtilisin/kexin type 9 J Thorac Dis 2017 Jan 9 1 E78 E82
Search in Google Scholar Back to article
Ooi EM Watts GF Chan DC Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus Arterioscler Thromb Vasc Biol 2015 Dec 35 12 2686 93
Search in Google Scholar Back to article
Viney NJ van Capelleveen JC Geary RS Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials Lancet 2016 Nov 5 388 10057 2239 53
Search in Google Scholar Back to article
Stefanutti C Thompson GR Lipoprotein apheresis in the management of familial hypercholesterolaemia: historical perspective and recent advances Curr Atheroscler Rep 2015 Jan 17 1 465
Search in Google Scholar Back to article
Gaudet D Alexander VJ Baker BF Antisense Inhibition of Apolipo-protein C-III in Patients with Hypertriglyceridemia N Engl J Med 2015 Jul 30 373 5 438 47
Search in Google Scholar Back to article
Dewey FE Gusarova V Dunbar RL Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease N Engl J Med 2017 Jul 20 377 3 211 21
Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.14797/mdcj-15-1-32 | Journal eISSN: 1947-6108

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Language: English

Page range: 32 - 38

Published on: Jan 1, 2019

Published by: Houston Methodist DeBakey Heart & Vascular Center

In partnership with: Paradigm Publishing Services

Keywords:

© 2019 Xiaoming Jia, Patrick Lorenz, Christie M. Ballantyne, published by Houston Methodist DeBakey Heart & Vascular Center
This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 License.

Volume 15 (2019): Issue 1