Efficacy and safety of add on therapies in patients with hypercholesterolemia undergoing statin therapy

References

• Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111–188.
   PubMed Web of Science ®Google Scholar
• Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722.
   PubMed Web of Science ®Google Scholar
• Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–2107.
   PubMed Web of Science ®Google Scholar
• Landmesser U, Chapman MJ, Farnier M, et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur Heart J. 2017;38(29):2245–2255.
   PubMed Web of Science ®Google Scholar
• Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 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;70(14):1785–1822.
   PubMed Web of Science ®Google Scholar
• Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;139(25):e1082–e1143.
   PubMed Web of Science ®Google Scholar
• Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–1297.
   PubMed Web of Science ®Google Scholar
• Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis. JAMA. 2018;319(15):1566–1579.
   PubMed Web of Science ®Google Scholar
• Ference BA, Ginsberg HN, Graham I, et al. 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. 2017;38(32):2459–2472.
   PubMed Web of Science ®Google Scholar
• Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease. Circ Res. 2016;118(4):547–563.
   PubMed Web of Science ®Google Scholar
• Ference BA, Kastelein JJP, Ray KK, et al. Association of triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants with risk of coronary heart disease. JAMA. 2019;321(4):364–373.
   PubMed Web of Science ®Google Scholar
• Ridker PM. Clinician’s guide to reducing inflammation to reduce atherothrombotic risk: JACC review topic of the week. J Am Coll Cardiol. 2018;72(25):3320–3331.
   PubMed Web of Science ®Google Scholar
• Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014;129(9):1022–1032.
   PubMed Web of Science ®Google Scholar
• Yamashita S, Masuda D, Matsuzawa Y. Did we abandon probucol too soon? Curr Opin Lipidol. 2015;26(4):304–316.
   PubMed Web of Science ®Google Scholar
• Kim BJ, Lee EJ, Kwon SU, et al. Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. Lancet Neurol. 2018;17(6):509–518.
   PubMed Web of Science ®Google Scholar
• Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B–26B.
   PubMed Web of Science ®Google Scholar
• Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245–1255.
   PubMed Web of Science ®Google Scholar
• The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA. 1975;231(4):360–381.
   PubMed Web of Science ®Google Scholar
• Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–2267.
   PubMed Web of Science ®Google Scholar
• Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–212.
   PubMed Web of Science ®Google Scholar
• The Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251(3):365–374.
   PubMed Web of Science ®Google Scholar
• The Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984;251(3):351–364.
   PubMed Web of Science ®Google Scholar
• The Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial. Results of 6 years of post-trial follow-up. The lipid research clinics investigators. Arch Intern Med. 1992;152(7):1399–1410.
   PubMedGoogle Scholar
• Schaefer EJ, Lamon-Fava S, Jenner JL, et al. Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid research clinics coronary primary prevention trial. JAMA. 1994;271(13):999–1003.
   PubMed Web of Science ®Google Scholar
• Mazidi M, Rezaie P, Karimi E, et al. The effects of bile acid sequestrants on lipid profile and blood glucose concentrations: A systematic review and meta-analysis of randomized controlled trials. Int J Cardiol. 2017;227:850–857.
   PubMed Web of Science ®Google Scholar
• Brunetti L, DeSantis EH. Patient tolerance and acceptance of colesevelam hydrochloride: focus on type-2 diabetes mellitus. P T. 2015;40(1):62–67.
   PubMedGoogle Scholar
• He L, Wickremasingha P, Lee J, et al. Lack of effect of colesevelam HCl on the single-dose pharmacokinetics of aspirin, atenolol, enalapril, phenytoin, rosiglitazone, and sitagliptin. Diabetes Res Clin Pract. 2014;104(3):401–409.
   PubMed Web of Science ®Google Scholar
• Bays HE, Moore PB, Drehobl MA, et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther. 2001;23(8):1209–1230.
   PubMed Web of Science ®Google Scholar
• Davis HR, Veltri EP. Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia. J Atheroscler Thromb. 2007;14(3):99–108.
   PubMed Web of Science ®Google Scholar
• Gagne C, Gaudet D, Bruckert E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation. 2002;105(21):2469–2475.
   PubMed Web of Science ®Google Scholar
• Yamamoto A, Harada-Shiba M, Endo M, et al. The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy. Atherosclerosis. 2006;186(1):126–131.
   PubMed Web of Science ®Google Scholar
• Couture P, Lamarche B. Ezetimibe and bile acid sequestrants: impact on lipoprotein metabolism and beyond. Curr Opin Lipidol. 2013;24(3):227–232.
   PubMed Web of Science ®Google Scholar
• Salen G, von Bergmann K, Lutjohann D, et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation. 2004;109(8):966–971.
   PubMed Web of Science ®Google Scholar
• Musliner T, Cselovszky D, Sirah W, et al. Efficacy and safety of ezetimibe 40 mg vs. ezetimibe 10 mg in the treatment of patients with homozygous sitosterolaemia. Int J Clin Pract. 2008;62(7):995–1000.
   PubMed Web of Science ®Google Scholar
• Phan BA, Dayspring TD, Toth PP. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415–427.
   PubMedGoogle Scholar
• Pandor A, Ara RM, Tumur I, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009;265(5):568–580.
   PubMed Web of Science ®Google Scholar
• Guyton JR, Betteridge DJ, Farnier M, et al. Achievement of recommended lipid and lipoprotein levels with combined ezetimibe/statin therapy versus statin alone in patients with and without diabetes. Diab Vasc Dis Res. 2011;8(2):160–172.
   PubMed Web of Science ®Google Scholar
• Leiter LA, Betteridge DJ, Farnier M, et al. Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes Obes Metab. 2011;13(7):615–628.
   PubMed Web of Science ®Google Scholar
• Pearson TA, Ballantyne CM, Veltri E, et al. Pooled analyses of effects on C-reactive protein and low density lipoprotein cholesterol in placebo-controlled trials of ezetimibe monotherapy or ezetimibe added to baseline statin therapy. Am J Cardiol. 2009;103(3):369–374.
   PubMed Web of Science ®Google Scholar
• Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358(14):1431–1443.
   PubMed Web of Science ®Google Scholar
• Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359(13):1343–1356.
   PubMed Web of Science ®Google Scholar
• Fleg JL, Mete M, Howard BV, et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol. 2008;52(25):2198–2205.
   PubMed Web of Science ®Google Scholar
• Meaney A, Ceballos G, Asbun J, et al. The VYtorin on Carotid intima-media thickness and overall arterial rigidity (VYCTOR) study. J Clin Pharmacol. 2009;49(7):838–847.
   PubMed Web of Science ®Google Scholar
• Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med. 2009;361(22):2113–2122.
   PubMed Web of Science ®Google Scholar
• Baigent C, Landray MJ, Reith C, et al. 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;377(9784):2181–2192.
   PubMed Web of Science ®Google Scholar
• Murphy SA, Cannon CP, Blazing MA, et al. Reduction in total cardiovascular events with Ezetimibe/Simvastatin post-acute coronary syndrome: the IMPROVE-IT trial. J Am Coll Cardiol. 2016;67(4):353–361.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Cannon CP, Blazing MA, et al. Benefit of adding Ezetimibe to Statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved reduction of outcomes: Vytorin efficacy international trial). Circulation. 2018;137(15):1571–1582.
   PubMed Web of Science ®Google Scholar
• Eisen A, Cannon CP, Blazing MA, et al. The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial. Eur Heart J. 2016;37(48):3576–3584.
   PubMed Web of Science ®Google Scholar
• Bohula EA, Wiviott SD, Giugliano RP, et al. Prevention of stroke with the addition of Ezetimibe to Statin therapy in patients with acute coronary syndrome in IMPROVE-IT (Improved reduction of outcomes: Vytorin efficacy international trial). Circulation. 2017;136(25):2440–2450.
   PubMed Web of Science ®Google Scholar
• Kosoglou T, Statkevich P, Johnson-Levonas AO, et al. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467–494.
   PubMed Web of Science ®Google Scholar
• de Waart DR, Vlaming ML, Kunne C, et al. Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009;37(8):1698–1702.
   PubMed Web of Science ®Google Scholar
• Lambert G, Sjouke B, Choque B, et al. The PCSK9 decade. J Lipid Res. 2012;53(12):2515–2524.
   PubMed Web of Science ®Google Scholar
• Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data. Expert Opin Drug Saf. 2019;18(7):611–621.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376(16):1527–1539.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Tardif JC, Amarenco P, et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N Engl J Med. 2017;376(16):1517–1526.
   PubMed Web of Science ®Google Scholar
• Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366(12):1108–1118.
   PubMed Web of Science ®Google Scholar
• Roth EM, Diller P. Alirocumab for hyperlipidemia: physiology of PCSK9 inhibition, pharmacodynamics and Phase I and II clinical trial results of a PCSK9 monoclonal antibody. Future Cardiol. 2014;10(2):183–199.
   PubMedGoogle Scholar
• Gaudet D, Kereiakes DJ, McKenney JM, et al. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014;114(5):711–715.
   PubMed Web of Science ®Google Scholar
• Roth EM. Alirocumab for hyperlipidemia: ODYSSEY Phase III clinical trial results and US FDA approval indications. Future Cardiol. 2016;12(2):115–128.
   PubMed Web of Science ®Google Scholar
• Tomlinson B, Hu M, Zhang Y, et al. Alirocumab for the treatment of hypercholesterolemia. Expert Opin Biol Ther. 2017;17(5):633–643.
   PubMed Web of Science ®Google Scholar
• Ray KK, Ginsberg HN, Davidson MH, et al. Reductions in atherogenic lipids and major cardiovascular events: a pooled analysis of 10 ODYSSEY trials comparing alirocumab to control. Circulation. 2016;134(24):1931-1943.
   Web of Science ®Google Scholar
• Stein EA, Wasserman SM, Dias CS, et al. AMG-145. Drugs Future. 2013;38(7):451–459.
   Web of Science ®Google Scholar
• Stein EA, Giugliano RP, Koren MJ, et al. Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials. Eur Heart J. 2014;35(33):2249–2259.
   PubMed Web of Science ®Google Scholar
• Langslet G, Emery M, Wasserman SM. Evolocumab (AMG 145) for primary hypercholesterolemia. Expert Rev Cardiovasc Ther. 2015;13(5):477–488.
   PubMed Web of Science ®Google Scholar
• Tomlinson B, Hu M, Zhang Y, et al. Evolocumab for the treatment of hypercholesterolemia. Expert Opin Biol Ther. 2017;17(11):1447–1461.
   PubMed Web of Science ®Google Scholar
• Raal FJ, Hovingh GK, Blom D, et al. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017;5(4):280–290.
   PubMed Web of Science ®Google Scholar
• Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):341–350.
   PubMed Web of Science ®Google Scholar
• Raal FJ, Giugliano RP, Sabatine MS, et al. PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor’s role. J Lipid Res. 2016;57(6):1086–1096.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–1509.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Keech A, Murphy SA, et al. Clinical efficacy and safety of evolocumab in high-risk patients receiving a statin: secondary analysis of patients with low LDL cholesterol levels and in those already receiving a maximal-potency statin in a randomized clinical trial. JAMA Cardiol. 2017;2(12):1385–1391.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Pedersen TR, Park JG, et al. 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. 2017;390(10106):1962–1971.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, De Ferrari GM, Giugliano RP, et al. Clinical benefit of evolocumab by severity and extent of coronary artery disease: analysis from FOURIER. Circulation. 2018;138(8):756–766.
   PubMed Web of Science ®Google Scholar
• Bonaca MP, Nault P, Giugliano RP, et al. 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(4):338–350.
   PubMed Web of Science ®Google Scholar
• Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5(12):941–950.
   PubMed Web of Science ®Google Scholar
• Bohula EA, Giugliano RP, Leiter LA, et al. Inflammatory and cholesterol risk in the FOURIER trial. Circulation. 2018;138(2):131–140.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377(7):633–643.
   PubMed Web of Science ®Google Scholar
• Frank-Kamenetsky M, Grefhorst A, Anderson NN, et al. Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A. 2008;105(33):11915–11920.
   PubMed Web of Science ®Google Scholar
• Nair JK, Willoughby JL, Chan A, et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc. 2014;136(49):16958–16961.
   PubMed Web of Science ®Google Scholar
• Fitzgerald K, White S, Borodovsky A, et al. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. N Engl J Med. 2017;376(1):41–51.
   PubMed Web of Science ®Google Scholar
• Stoekenbroek RM, Kallend D, Wijngaard PL, et al. Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program. Future Cardiol. 2018;14(6):433–442.
   PubMed Web of Science ®Google Scholar
• Nishikido T, Ray KK. Inclisiran for the treatment of dyslipidemia. Expert Opin Investig Drugs. 2018;27(3):287–294.
   PubMed Web of Science ®Google Scholar
• Ray KK, Landmesser U, Leiter LA, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;376(15):1430–1440.
   PubMed Web of Science ®Google Scholar
• Ray KK, Stoekenbroek RM, Kallend D, et al. Effect of an siRNA therapeutic targeting PCSK9 on atherogenic lipoproteins. Circulation. 2018;138(13):1304–1316.
   PubMed Web of Science ®Google Scholar
• Ray KK, Stoekenbroek RM, Kallend D, et al. Effect of 1 or 2 doses of inclisiran on low-density lipoprotein cholesterol levels: one-year follow-up of the ORION-1 randomized clinical trial. JAMA Cardiol. 2019;4(11):1067–1075.
   PubMed Web of Science ®Google Scholar
• Raal FJ, Kallend D, Ray KK, et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med. 2020;382(16):1520–1530.
   PubMed Web of Science ®Google Scholar
• Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507–1519.
   PubMed Web of Science ®Google Scholar
• Bempedoic Acid FDA approval. Drugs@FDA: FDA-approved drugs. 2020 Feb 21 [cited 2020 Mar 1]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211616
   Google Scholar
• Penson P, McGowan M, Banach M. Evaluating bempedoic acid for the treatment of hyperlipidaemia. Expert Opin Investig Drugs. 2017;26(2):251–259.
   PubMed Web of Science ®Google Scholar
• Saeed A, Ballantyne CM. Bempedoic acid (ETC-1002): a current review. Cardiol Clin. 2018;36(2):257–264.
   PubMed Web of Science ®Google Scholar
• Pinkosky SL, Newton RS, Day EA, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016;7:13457.
   PubMed Web of Science ®Google Scholar
• Ference BA, Ray KK, Catapano AL, et al. Mendelian randomization study of ACLY and cardiovascular disease. N Engl J Med. 2019;380(11):1033–1042.
   PubMed Web of Science ®Google Scholar
• Nikolic D, Mikhailidis DP, Davidson MH, et al. ETC-1002: a future option for lipid disorders? Atherosclerosis. 2014;237(2):705–710.
   PubMed Web of Science ®Google Scholar
• Bilen O, Ballantyne CM. Bempedoic acid (ETC-1002): an investigational inhibitor of ATP citrate lyase. Curr Atheroscler Rep. 2016;18(10):61.
   PubMed Web of Science ®Google Scholar
• Ballantyne CM, Davidson MH, Macdougall DE, et al. 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;62(13):1154–1162.
   PubMed Web of Science ®Google Scholar
• Thompson PD, MacDougall DE, Newton RS, et al. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance. J Clin Lipidol. 2016;10(3):556–567.
   PubMed Web of Science ®Google Scholar
• Goldberg AC, Leiter LA, Stroes ESG, et al. 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. 2019;322(18):1780–1788.
   PubMed Web of Science ®Google Scholar
• Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380(11):1022–1032.
   PubMed Web of Science ®Google Scholar
• Laufs U, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J Am Heart Assoc. 2019;8(7):e011662.
   PubMed Web of Science ®Google Scholar
• Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018;277:195–203.
   PubMed Web of Science ®Google Scholar
• Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2019;27(6):593–603.
   PubMed Web of Science ®Google Scholar
• NEXLETOL (bempedoic acid) prescribing information. 2020 Feb [cited 2020 May 1]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/211616s000lbl.pdf
   Google Scholar
• Chapman MJ, Redfern JS, McGovern ME, et al. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010;126(3):314–345.
   PubMed Web of Science ®Google Scholar
• Okopien B, Buldak L, Boldys A. Fibrates in the management of atherogenic dyslipidemia. Expert Rev Cardiovasc Ther. 2017;15(12):913–921.
   PubMed Web of Science ®Google Scholar
• Willson TM, Brown PJ, Sternbach DD, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43(4):527–550.
   PubMed Web of Science ®Google Scholar
• Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–1574.
   PubMed Web of Science ®Google Scholar
• Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849–1861.
   PubMed Web of Science ®Google Scholar
• Elam MB, Ginsberg HN, Lovato LC, et al. Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes. JAMA Cardiol. 2017;2(4):370–380.
   PubMed Web of Science ®Google Scholar
• Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–1884.
   PubMed Web of Science ®Google Scholar
• Bruckert E, Labreuche J, Deplanque D, et al. Fibrates effect on cardiovascular risk is greater in patients with high triglyceride levels or atherogenic dyslipidemia profile: a systematic review and meta-analysis. J Cardiovasc Pharmacol. 2011;57(2):267–272.
   PubMed Web of Science ®Google Scholar
• Jun M, Zhu B, Tonelli M, et al. Effects of fibrates in kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2012;60(20):2061–2071.
   PubMed Web of Science ®Google Scholar
• Simental-Mendia LE, Simental-Mendia M, Sanchez-Garcia A, et al. Effect of fibrates on glycemic parameters: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res. 2018;132:232–241.
   PubMed Web of Science ®Google Scholar
• Prueksaritanont T, Tang C, Qiu Y, et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos. 2002;30(11):1280–1287.
   PubMed Web of Science ®Google Scholar
• Davidson MH. Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions. Expert Opin Drug Saf. 2006;5(1):145–156.
   PubMed Web of Science ®Google Scholar
• Tomlinson B, Chan P, Zhang Y, et al. Pharmacokinetics of current and emerging treatments for hypercholesterolemia. Expert Opin Drug Metab Toxicol. 2020;16(5):371–385.
   PubMed Web of Science ®Google Scholar
• Fruchart JC, Santos RD, Aguilar-Salinas C, et al. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha) paradigm: conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation. Cardiovasc Diabetol. 2019;18(1):71.
   PubMed Web of Science ®Google Scholar
• Pradhan AD, Paynter NP, Everett BM, et al. Rationale and design of the pemafibrate to reduce cardiovascular outcomes by reducing triglycerides in patients with diabetes (PROMINENT) study. Am Heart J. 2018;206:80–93.
   PubMed Web of Science ®Google Scholar
• Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.
   PubMed Web of Science ®Google Scholar
• FDA approves use of Vascepa (icosapent ethyl) to reduce risk of cardiovascular events in certain adult patient groups.2019 Dec 13 [cited 2020 Mar 1]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups1Mar2020
   Google Scholar
• Bays HE, Ballantyne CM, Doyle RT Jr., et al. Icosapent ethyl: eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies. Prostaglandins Other Lipid Mediat. 2016;125:57–64.
   PubMed Web of Science ®Google Scholar
• Mason RP, Libby P, Bhatt DL. Emerging mechanisms of cardiovascular protection for the omega-3 fatty acid eicosapentaenoic acid. Arterioscler Thromb Vasc Biol. 2020;40(5):1135–1147.
   PubMed Web of Science ®Google Scholar
• Sahebkar A, Simental-Mendia LE, Mikhailidis DP, et al. Effect of omega-3 supplements on plasma apolipoprotein C-III concentrations: a systematic review and meta-analysis of randomized controlled trials. Ann Med. 2018;50(7):565–575.
   PubMed Web of Science ®Google Scholar
• Ballantyne CM, Braeckman RA, Soni PN. Icosapent ethyl for the treatment of hypertriglyceridemia. Expert Opin Pharmacother. 2013;14(10):1409–1416.
   PubMed Web of Science ®Google Scholar
• Oesterle A, Liao JK. The pleiotropic effects of statins - from coronary artery disease and stroke to atrial fibrillation and ventricular tachyarrhythmia. Curr Vasc Pharmacol. 2019;17(3):222–232.
   PubMed Web of Science ®Google Scholar
• Samsoondar JP, Burke AC, Sutherland BG, et al. Prevention of diet-induced metabolic dysregulation, inflammation, and atherosclerosis in Ldlr(-/-) mice by treatment with the ATP-citrate lyase inhibitor bempedoic acid. Arterioscler Thromb Vasc Biol. 2017;37(4):647–656.
   PubMed Web of Science ®Google Scholar
• Cicero AFG, Pontremoli R, Fogacci F, et al. Effect of bempedoic acid on serum uric acid and related outcomes: a systematic review and meta-analysis of the available phase 2 and phase 3 clinical studies. Drug Saf. 2020. DOI: 10.1007/s40264-020-00931-6
   PubMed Web of Science ®Google Scholar
• Kalogirou M, Tsimihodimos V, Elisaf M. Pleiotropic effects of ezetimibe: do they really exist? Eur J Pharmacol. 2010;633(1–3):62–70.
   PubMed Web of Science ®Google Scholar
• Pesaro AE, Serrano CV Jr., Fernandes JL, et al. Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin. Int J Cardiol. 2012;158(3):400–404.
   PubMed Web of Science ®Google Scholar
• Karagiannis AD, Liu M, Toth PP, et al. Pleiotropic anti-atherosclerotic effects of PCSK9 inhibitorsfrom molecular biology to clinical translation. Curr Atheroscler Rep. 2018;20(4):20.
   PubMed Web of Science ®Google Scholar
• Pasta A, Cremonini AL, Pisciotta L, et al. PCSK9 inhibitors for treating hypercholesterolemia. Expert Opin Pharmacother. 2020;21(3):353–363.
   PubMed Web of Science ®Google Scholar
• Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370(9600):1687–1697.
   PubMed Web of Science ®Google Scholar
• Noonan JE, Jenkins AJ, Ma JX, et al. An update on the molecular actions of fenofibrate and its clinical effects on diabetic retinopathy and other microvascular end points in patients with diabetes. Diabetes. 2013;62(12):3968–3975.
   PubMed Web of Science ®Google Scholar
• Gupta M, Blumenthal C, Chatterjee S, et al. Novel emerging therapies in atherosclerosis targeting lipid metabolism. Expert Opin Investig Drugs. 2020;1–12. DOI: 10.1080/13543784.2020.1764937
   Web of Science ®Google Scholar
• Gusarova V, Alexa CA, Wang Y, et al. ANGPTL3 blockade with a human monoclonal antibody reduces plasma lipids in dyslipidemic mice and monkeys. J Lipid Res. 2015;56(7):1308–1317.
   PubMed Web of Science ®Google Scholar
• Dewey FE, Gusarova V, Dunbar RL, et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. N Engl J Med. 2017;377(3):211–221.
   PubMed Web of Science ®Google Scholar
• Banerjee P, Chan KC, Tarabocchia M, et al. Functional analysis of LDLR (Low-density lipoprotein receptor) variants in patient lymphocytes to assess the effect of evinacumab in homozygous familial hypercholesterolemia patients with a spectrum of LDLR activity. Arterioscler Thromb Vasc Biol. 2019;39(11):2248–2260.
   PubMed Web of Science ®Google Scholar
• Graham MJ, Lee RG, Brandt TA, et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. N Engl J Med. 2017;377(3):222–232.
   PubMed Web of Science ®Google Scholar
• Hegele RA, Tsimikas S. Lipid-lowering agents. Circ Res. 2019;124(3):386–404.
   PubMed Web of Science ®Google Scholar
• Paik J, Duggan S. Volanesorsen: first global approval. Drugs. 2019;79(12):1349–1354.
   PubMed Web of Science ®Google Scholar
• Witztum JL, Gaudet D, Freedman SD, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019;381(6):531–542.
   PubMed Web of Science ®Google Scholar
• Alexander VJ, Xia S, Hurh E, et al. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019;40(33):2785–2796.
   PubMed Web of Science ®Google Scholar
• Tsimikas S. RNA-targeted therapeutics for lipid disorders. Curr Opin Lipidol. 2018;29(6):459–466.
   PubMed Web of Science ®Google Scholar
• Viney NJ, van Capelleveen JC, Geary RS, et al. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016;388(10057):2239–2253.
   PubMed Web of Science ®Google Scholar
• Gibson CM, Kerneis M, Yee MK, et al. The CSL112-2001 trial: safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction. Am Heart J. 2019;208:81–90.
   PubMed Web of Science ®Google Scholar
• Gibson MC, Korjian S, Tricoci P, et al. Safety and tolerability of CSL112, a reconstituted, infusible, plasma-derived apolipoprotein A-I, after acute myocardial infarction: the AEGIS-I trial (ApoA-I event reducing in ischemic syndromes I). Circulation. 2016;134(24):1918–1930.
   PubMed Web of Science ®Google Scholar
• Shamburek RD, Bakker-Arkema R, Auerbach BJ, et al. Familial lecithin:cholesterol acyltransferase deficiency: first-in-human treatment with enzyme replacement. J Clin Lipidol. 2016;10(2):356–367.
   PubMed Web of Science ®Google Scholar
• Ossoli A, Simonelli S, Varrenti M, et al. Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) rescues defective HDL (High-Density Lipoprotein)-mediated endothelial protection in acute coronary syndrome. Arterioscler Thromb Vasc Biol. 2019;39(5):915–924.
   PubMed Web of Science ®Google Scholar
• Danchin N, Almahmeed W, Al-Rasadi K, et al. Achievement of low-density lipoprotein cholesterol goals in 18 countries outside Western Europe: the International ChoLesterol management Practice Study (ICLPS). Eur J Prev Cardiol. 2018;25(10):1087–1094.
   PubMed Web of Science ®Google Scholar
• Ferrieres J, De Ferrari GM, Hermans MP, et al. Predictors of LDL-cholesterol target value attainment differ in acute and chronic coronary heart disease patients: results from DYSIS II Europe. Eur J Prev Cardiol. 2018;25(18):1966–1976.
   PubMed Web of Science ®Google Scholar
• Robinson JG, Huijgen R, Ray K, et al. Determining when to add nonstatin therapy: a quantitative approach. J Am Coll Cardiol. 2016;68(22):2412–2421.
   PubMed Web of Science ®Google Scholar
• Baigent C, Blackwell L, Emberson J, et al. 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;376(9753):1670–1681.
   PubMed Web of Science ®Google Scholar
• Laufs U, Descamps OS, Catapano AL, et al. Understanding IMPROVE-IT and the cardinal role of LDL-C lowering in CVD prevention. Eur Heart J. 2014;35(30):1996–2000.
   PubMed Web of Science ®Google Scholar
• Annemans L, Packard CJ, Briggs A, et al. ‘Highest risk-highest benefit’ strategy: a pragmatic, cost-effective approach to targeting use of PCSK9 inhibitor therapies. Eur Heart J. 2018;39(27):2546–2550.
   PubMed Web of Science ®Google Scholar
• Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–742.
   PubMed Web of Science ®Google Scholar
• Ference BA, Robinson JG, Brook RD, et al. Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Engl J Med. 2016;375(22):2144–2153.
   PubMed Web of Science ®Google Scholar
• Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–2561.
   PubMed Web of Science ®Google Scholar
• Zhang X, Liu J, Wang M, et al. Twenty-year epidemiologic study on LDL-C levels in relation to the risks of atherosclerotic event, hemorrhagic stroke, and cancer death among young and middle-aged population in China. J Clin Lipidol. 2018;12(5):1179–1189 e1174.
   PubMed Web of Science ®Google Scholar
• Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI working group recommendations to reduce Lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71(2):177–192.
   PubMed Web of Science ®Google Scholar