New Therapeutic Approaches to the Treatment of Dyslipidemia 2: LDL-C and Lp(a)
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Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). There are abundant and unequivocal data to indicate that low-density lipoproteins (LDL) are a cause of ASCVD. Reduction of plasma low-density lipoprotein cholesterol (LDL-C) by medical therapy such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have proven to significantly reduce the risk of cardiovascular events. However, for many reasons, many patients are not able to achieve LDL-C levels recommended by guidelines on currently available therapies. This has led to the development of new drugs lowering LDL-C, such as inclisiran, bempedoic acid, and evinacumab, in the hope of reducing cardiovascular (CV) risk. Drugs targeting lipoprotein (a) (Lp[a]) also have a role in the prevention of atherosclerosis, with genetic studies having established that 20%–30% of the human population inherits plasma Lp(a) levels in the atherogenic range. In this paper, we will review the recent progress made in the approaches to LDL-C and Lp(a) therapeutic modulation.
Abstract
Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). There are abundant and unequivocal data to indicate that low-density lipoproteins (LDL) are a cause of ASCVD. Reduction of plasma low-density lipoprotein cholesterol (LDL-C) by medical therapy such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have proven to significantly reduce the risk of cardiovascular events. However, for many reasons, many patients are not able to achieve LDL-C levels recommended by guidelines on currently available therapies. This has led to the development of new drugs lowering LDL-C, such as inclisiran, bempedoic acid, and evinacumab, in the hope of reducing cardiovascular (CV) risk. Drugs targeting lipoprotein (a) (Lp[a]) also have a role in the prevention of atherosclerosis, with genetic studies having established that 20%–30% of the human population inherits plasma Lp(a) levels in the atherogenic range. In this paper, we will review the recent progress made in the approaches to LDL-C and Lp(a) therapeutic modulation.
참고문헌 (41)
- Virani SS, "Heart disease and stroke statistics-2021 update : a report from the American Heart Association", Circulation, 143, pp.e254~e743 (2021)
- Nordestgaard BG, "Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease : new insights from epidemiology, genetics, and biology", Circ Res, 118, pp.547~563 (2016)
- Grundy SM, "2018 AHA", ACC, AAPA, pp.ABC, ACPM[DOI]
- Mach F, "2019 ESC", EAS guidelines for the management of dyslipidaemias : lipid modification to reduce cardiovascular risk, 2020, pp.41, 111~188
- Cholesterol Treatment Trialists’(CTT)Collaboration, "Efficacy and safety of LDL-lowering therapy among men and women : meta-analysis of individual data from 174, 000 participants in 27 randomised trials", Lancet, 385, pp.1397~1405 (2015)
- Khan SU, "Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies : systematic review and meta-analysis of trials", Eur J Prev Cardiol, 27, pp.1255~1268 (2020)
- Presta V, "Achievement of low density lipoprotein(LDL)cholesterol targets in primary and secondary prevention : Analysis of a large real practice database in Italy", Atherosclerosis, 285, pp.40~48 (2019)
- Scheidt-Nave C, "Prevalence of dyslipidemia among adults in Germany : results of the German Health Interview and Examination Survey for Adults(DEGS 1)", Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 56, pp.661~667 (2013)
- Lippi G, "Biochemical correlates of lipoprotein(a)in a general adult population. Possible implications for cardiovascular risk assessment", J Thromb Thrombolysis, 27, pp.44~47 (2009)
- Ference BA, "Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel", Eur Heart J, 38, pp.2459~2472 (2017)
- Cannon CP, "Ezetimibe added to statin therapy after acute coronary syndromes", N Engl J Med, 372, pp.2387~2397 (2015)
- Giugliano RP, "Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab : a prespecified secondary analysis of the FOURIER trial", Lancet, 390, pp.1962~1971 (2017)
- Schwartz GG, "Alirocumab and cardiovascular outcomes after acute coronary syndrome", N Engl J Med, 379, pp.2097~2107 (2018)
- Ridker PM, "Percent reduction in LDL cholesterol following high-intensity statin therapy : potential implications for guidelines and for the prescription of emerging lipid-lowering agents", Eur Heart J, 37, pp.1373~1379 (2016)
- Stroes ES, "Statin-associated muscle symptoms : impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management", Eur Heart J, 36, pp.1012~1022 (2015)
- Mancini GB, "Diagnosis, prevention, and management of statin adverse effects and intolerance : Canadian Consensus Working Group Update(2016)", Can J Cardiol, 32, pp.S35~S65 (2016)
- Yusuf S, "Cholesterol lowering in intermediate-risk persons without cardiovascular disease", N Engl J Med, 374, pp.2021~2031 (2016)
- Urban D, "Targeting the proprotein convertase subtilisin", kexin type 9 for the treatment of dyslipidemia and atherosclerosis, 2013, pp.62, 1401~1408
- Frank-Kamenetsky M, "Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates", Proc Natl Acad Sci U S A, 105, pp.11915~11920 (2008)
- Fitzgerald K, "A highly durable RNAi therapeutic inhibitor of PCSK9", N Engl J Med, 376, pp.41~51 (2017)
- Ray KK, "Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol", N Engl J Med, 376, pp.1430~1440 (2017)
- Pinkosky SL, "Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis", Nat Commun, 7, pp.13457~ (2016)
- Ference BA, "Mendelian randomization study of ACLY and cardiovascular disease", N Engl J Med, 380, pp.1033~1042 (2019)
- Goldberg AC, "Effect of bempedoic acid vs placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease : the CLEAR Wisdom randomized clinical trial", JAMA, 322, pp.1780~1788 (2019)
- Laufs U, "Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance", J Am Heart Assoc, 8, pp.e011662~ (2019)
- Ballantyne CM, "Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia : A randomized, placebo-controlled study", Atherosclerosis, 277, pp.195~203 (2018)
- Ray KK, "Safety and efficacy of bempedoic acid to reduce LDL cholesterol", N Engl J Med, 380, pp.1022~1032 (2019)
- Berg K, "A new serum type system in man--the Lp system", Acta Pathol Microbiol Scand, 59, pp.369~382 (1963)
- Schmidt K, "Structure, function, and genetics of lipoprotein(a)", J Lipid Res, 57, pp.1339~1359 (2016)
- Tsimikas S, "Lipoprotein(a)reduction in persons with cardiovascular disease", N Engl J Med, 382, pp.244~255 (2020)
- Tsimikas S, "A test in context : lipoprotein(a) : diagnosis, prognosis, controversies, and emerging therapies", J Am Coll Cardiol, 69, pp.692~711 (2017)
- Khera AV, "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, 129, pp.635~642 (2014)
- Nordestgaard BG, "Lipoprotein(a)as a cardiovascular risk factor : current status", Eur Heart J, 31, pp.2844~2853 (2010)
- Varvel S, "Prevalence of elevated Lp(a)mass levels and patient thresholds in 532 359 patients in the United States", Arterioscler Thromb Vasc Biol, 36, pp.2239~2245 (2016)
- Capoulade R, "Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis", J Am Coll Cardiol, 66, pp.1236~1246 (2015)
- van Buuren F, "Incidence of elevated lipoprotein(a)levels in a large cohort of patients with cardiovascular disease", Clin Res Cardiol Suppl, 12, pp.55~59 (2017)
- Raal FJ, "Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia(TESLA Part B) : a randomised, double-blind, placebo-controlled trial", Lancet, 385, pp.341~350 (2015)
- Crooke ST, "RNA-targeted therapeutics", Cell Metab, 27, pp.714~739 (2018)
- Viney NJ, "Antisense oligonucleotides targeting apolipoprotein(a)in people with raised lipoprotein(a) : two randomised, double-blind, placebo-controlled, dose-ranging trials", Lancet, 388, pp.2239~2253 (2016)
- Koren MJ, "Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a)", Nat Med, 28, pp.96~103 (2022)
- O’Donoghue ML, "Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a)reduction-DOSE finding study(OCEAN(a)-DOSE)", Am Heart J, 251, pp.61~69 (2022)