CoChat
Sign Up
Cited by 73Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Lipid Lowering Drugs: Present Status and Future Developments

Open access
Ruscica, Massimiliano, Ferri, Nicola, Santos, Raul D., Sirtori, Cesare R., Corsini, Alberto·2021·Current Atherosclerosis Reports
DOI 10.1007/s11883-021-00918-3PMC PMC7946696
Open this paper in CoChat — free accountOpen PDF

Abstract

Purpose of review: Based on the recent data of the DA VINCI study, it is clear that, besides utilization of statins, there is a need to increase non-statin lipid lowering approaches to reduce the cardiovascular burden in patients at highest risk. Recent findings: For hypercholesterolemia, the small synthetic molecule bempedoic acid has the added benefit of selective liver activation, whereas inclisiran, a hepatic inhibitor of the PCSK9 synthesis, has comparable effects with PCSK9 monoclonal antibodies. For hypertriglyceridemia, cardiovascular benefit has been achieved by the use of icosapent ethyl, whereas results with pemafibrate, a selective agonist of PPAR-α, are eagerly awaited. In the era of RNA-based therapies, new options are offered to dramatically reduce levels of lipoprotein(a) (APO(a)L RX) and of triglycerides (ANGPTL3L RX and APOCIII-L Rx). Summary: Despite the demonstrated benefits of statins, a large number of patients still remain at significant risk because of inadequate LDL-C reduction or elevated blood triglyceride-rich lipoproteins or lipoprotein(a). The area of lipid modulating agents is still ripe with ideas and major novelties are to be awaited in the next few years.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s11883-021-00918-3

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The LDL-C lowering capability of inclisiran reaches approximately 45%, ranking it as one of the strongest lipid-lowering medications but falling short of the 60% reduction seen with PCSK9 monoclonal antibodies evolocumab and alirocumab.

    “The LDL-C lowering capability of Inclisiran reaches approximately 45% which ranks it as one of the strongest lipid-lowering medications but falls short of the 60% reduction seen with PCSK9 monoclonal antibodies evolocumab and alirocumab [47, 73].”

    From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [73]

    The “PCSK9 Inhibition by Silencing RNA” section reports a 44.3% time-averaged LDL-C reduction with inclisiran in ORION-9, supporting the approximately 45% figure. The paper calls inclisiran’s LDL-C-lowering effect powerful, but its “PCSK9 Inhibition by Monoclonal Antibodies” section does not give a 60% LDL-C reduction for evolocumab and alirocumab or establish the claimed potency ranking. Page numbers were not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Monoclonal antibodies achieve slightly higher LDL-C reductions (~60%) than inclisiran, while inclisiran's twice-yearly dosing may enhance adherence and long-term persistence in real-world settings.

    “While mAbs achieve slightly higher LDL-C reductions (~ 60%), inclisiran’s twice-yearly dosing may enhance adherence and long-term persistence in real-world settings.”

    From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [73]

    The 'PCSK9 Inhibition by Silencing RNA' section (page unavailable) reports roughly 50% LDL-C reductions with inclisiran and dosing every 180 days after the initial doses. The passages do not establish approximately 60% LDL-C reduction with monoclonal antibodies or say that inclisiran's schedule may improve real-world adherence or long-term persistence. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 126 · Cited by 73

Research works printed but not linked: 96

  1. [1]Goyal A Cho L Preventive cardiology and risk assessment: Beyond LDL Curr Atheroscler Rep 2020 22 10 56 32772179
  2. [2]Yusuf S Hawken S Ounpuu S Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study Lancet 2004 364 9438 937 952 15364185
  3. [3]Ference BA Ginsberg HN Graham I Ray KK Packard CJ Bruckert E Hegele RA Krauss RM Raal FJ Schunkert H Watts GF Borén J Fazio S Horton JD Masana L Nicholls SJ Nordestgaard BG van de Sluis B Taskinen MR Tokgözoğlu L Landmesser U Laufs U Wiklund O Stock JK Chapman MJ Catapano 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 28444290 PMC5837225
  4. [4]Boren J Chapman MJ Krauss RM Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel Eur Heart J 2020 41 24 2313 2330 32052833 PMC7308544
  5. [7]Grundy SM Stone NJ Bailey AL Beam C Birtcher KK Blumenthal RS Braun LT de Ferranti S Faiella-Tommasino J Forman DE Goldberg R Heidenreich PA Hlatky MA Jones DW Lloyd-Jones D Lopez-Pajares N Ndumele CE Orringer CE Peralta CA Saseen JJ Smith SC Jr Sperling L Virani SS Yeboah J 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 30586774 PMC7403606
  6. [8]Authors/Task Force M, Guidelines ESCCfP, Societies ESCNC 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk Atherosclerosis 2019 290 140 205 31591002
  7. [9]Matsuura Y Kanter JE Bornfeldt KE Highlighting residual atherosclerotic cardiovascular disease risk Arterioscler Thromb Vasc Biol 2019 39 1 e1 e9 30586334 PMC6310032
  8. [10]Reiner Z Hypertriglyceridaemia and risk of coronary artery disease Nat Rev Cardiol 2017 14 7 401 411 28300080
  9. [12]Nelson AJ Navar AM Mulder H Wojdyla D Philip S Granowitz C Peterson ED Pagidipati NJ Association between triglycerides and residual cardiovascular risk in patients with type 2 diabetes mellitus and established cardiovascular disease (from the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial) Am J Cardiol 2020 132 36 43 32773223
  10. [13]Sirtori CR Ruscica M Calabresi L Chiesa G Giovannoni R Badimon JJ HDL therapy today: from atherosclerosis, to stent compatibility to heart failure Ann Med 2019 51 7-8 345 359 31729238 PMC7877888
  11. [14]Zheng KH Kaiser Y van Olden CC Santos RD Dasseux JL Genest J Gaudet D Westerink J Keyserling C Verberne HJ Leitersdorf E Hegele RA Descamps OS Hopkins P Nederveen AJ Stroes ESG No benefit of HDL mimetic CER-001 on carotid atherosclerosis in patients with genetically determined very low HDL levels Atherosclerosis 2020 311 13 19 32919280
  12. [16]Schnitzler JG Hoogeveen RM Ali L Prange KHM Waissi F van Weeghel M Bachmann JC Versloot M Borrelli MJ Yeang C de Kleijn DPV Houtkooper RH Koschinsky ML de Winther MPJ Groen AK Witztum JL Tsimikas S Stroes ESG Kroon J Atherogenic lipoprotein(a) increases vascular glycolysis, thereby facilitating inflammation and leukocyte extravasation Circ Res 2020 126 10 1346 1359 32160811 PMC7208285
  13. [18]Sirtori CR The pharmacology of statins Pharmacol Res 2014 88 3 11 24657242
  14. [19]Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Bejot Y, Cabrejo L, Cha JK, Ducrocq G, Giroud M, Guidoux C, Hobeanu C, Kim YJ, Lapergue B, Lavallee PC, Lee BC, Lee KB, Leys D, Mahagne MH, Meseguer E, Nighoghossian N, Pico F, Samson Y, Sibon I, Steg PG, Sung SM, Touboul PJ, Touze E, Varenne O, Vicaut E, Yelles N, Bruckert E. Treat stroke to target investigators. a comparison of two LDL cholesterol targets after ischemic stroke. N Engl J Med. 2020 Jan 2;382(1):9.
  15. [20]Ferri N Grego MF Corsini A Ruscica M Proprotein convertase subtilisin/kexin type 9: an update on the cardiovascular outcome studies Eur Heart J Suppl 2020 22 Suppl E E64 E67 32523442 PMC7270917
  16. [22]Sever P, Gouni-Berthold I, Keech A, et al. LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial. Eur J Prev Cardiol. 2020:2047487320902750. 34298555
  17. [24]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 4 338 350 29133605
  18. [25]• Gencer B, Mach F, Murphy SA, et al. Efficacy of evolocumab on cardiovascular outcomes in patients with recent myocardial infarction: a prespecified secondary analysis from the FOURIER trial. JAMA Cardiol. 2020; The Authors provide evidence to aggressively lower low-density lipoprotein cholesterol levels in very high-risk patients, such as those with a recent myocardial infarction. PMC7240652 32432684
  19. [26]Wiviott SD Giugliano RP Morrow DA de Ferrari GM Lewis BS Huber K Kuder JF Murphy SA Forni DM Kurtz CE Honarpour N Keech AC Sever PS Pedersen TR Sabatine MS Effect of evolocumab on type and size of subsequent myocardial infarction: a prespecified analysis of the FOURIER randomized clinical trial JAMA Cardiol 2020 5 7 787 793 32347885 PMC7191470
  20. [27]Sabatine MS Leiter LA Wiviott SD Giugliano RP Deedwania P de Ferrari GM Murphy SA Kuder JF Gouni-Berthold I Lewis BS Handelsman Y Pineda AL Honarpour N Keech AC Sever PS Pedersen TR 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 28927706
  21. [28]Deedwania P, Murphy SA, Scheen A, et al. Efficacy and safety of PCSK9 inhibition with evolocumab in reducing cardiovascular events in patients with metabolic syndrome receiving statin therapy: secondary analysis from the FOURIER randomized clinical trial. JAMA Cardiol. 2021 Feb 1;6(2):139–47. PMC9426725 32785614
  22. [29]Giugliano RP Pedersen TR Saver JL Stroke prevention with the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis Stroke 2020 51 5 1546 1554 32312223
  23. [30]Sinnaeve PR Schwartz GG Wojdyla DM Alings M Bhatt DL Bittner VA Chiang CE Correa Flores RM Diaz R Dorobantu M Goodman SG Jukema JW Kim YU Pordy R Roe MT Sy RG Szarek M White HD Zeiher AM Steg PG for the ODYSSEY OUTCOMES Investigators Effect of alirocumab on cardiovascular outcomes after acute coronary syndromes according to age: an ODYSSEY OUTCOMES trial analysis Eur Heart J 2020 41 24 2248 2258 31732742 PMC7308542
  24. [31]Tunon J, Steg PG, Bhatt DL, et al. Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial. Eur Heart J. 2020 Nov 7;41(42):4114–23. PMC7700757 32820320
  25. [32]Jukema JW Zijlstra LE Bhatt DL Bittner VA Diaz R Drexel H Goodman SG Kim YU Pordy R Reiner Ž Roe MT Tse HF Montenegro Valdovinos PC White HD Zeiher AM Szarek M Schwartz GG Steg PG For the ODYSSEY OUTCOMES Investigators Effect of alirocumab on stroke in ODYSSEY OUTCOMES Circulation 2019 140 25 2054 2062 31707788 PMC6919220
  26. [33]Szarek M Steg PG DiCenso D Bhatt DL Bittner VA Budaj A Diaz R Goodman SG Gotcheva N Jukema JW Pordy R Roe MT Sourdille T White HD Xavier D Zeiher AM Schwartz GG Alirocumab reduces total hospitalizations and increases days alive and out of hospital in the ODYSSEY OUTCOMES Trial Circ Cardiovasc Qual Outcomes 2019 12 11 e005858 31707826
  27. [34]Marston NA Kamanu FK Nordio F Gurmu Y Roselli C Sever PS Pedersen TR Keech AC Wang H Lira Pineda A Giugliano RP Lubitz SA Ellinor PT Sabatine MS Ruff CT Predicting benefit from evolocumab therapy in patients with atherosclerotic disease using a genetic risk score: results from the FOURIER Trial Circulation 2020 141 8 616 623 31707849 PMC8058781
  28. [35]Damask A Steg PG Schwartz GG Szarek M Hagström E Badimon L Chapman MJ Boileau C Tsimikas S Ginsberg HN Banerjee P Manvelian G Pordy R Hess S Overton JD Lotta LA Yancopoulos GD Abecasis GR Baras A Paulding C On behalf of the Regeneron Genetics Center and the ODYSSEY OUTCOMES Investigators Patients with high genome-wide polygenic risk scores for coronary artery disease may receive greater clinical benefit from alirocumab treatment in the ODYSSEY OUTCOMES trial Circulation 2020 141 8 624 636 31707832
  29. [36]Marston NA Gurmu Y Melloni GEM Bonaca M Gencer B Sever PS Pedersen TR Keech AC Roselli C Lubitz SA Ellinor PT O’Donoghue ML Giugliano RP Ruff CT Sabatine MS The effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of venous thromboembolism Circulation 2020 141 20 1600 1607 32223429 PMC7469753
  30. [37]Ruscica M Tokgozoglu L Corsini A Sirtori CR PCSK9 inhibition and inflammation: a narrative review Atherosclerosis 2019 288 146 155 31404822
  31. [38]Ruscica M Corsini A Ferri N Banach M Sirtori CR Clinical approach to the inflammatory etiology of cardiovascular diseases Pharmacol Res 2020 159 104916 32445957 PMC7238995
  32. [39]Macchi C Sirtori CR Corsini A Santos RD Watts GF Ruscica M A new dawn for managing dyslipidemias: the era of rna-based therapies Pharmacol Res 2019 150 104413 31449975
  33. [40]Ruscica M Zimetti F Adorni MP Sirtori CR Lupo MG Ferri N Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: new therapeutic approaches for the treatment of atherogenic dyslipidemia Pharmacol Res 2020 153 104653 31931117
  34. [41]Brandts J Ray KK Small interfering RNA to proprotein convertase subtilisin/kexin type 9: transforming LDL-cholesterol-lowering strategies Curr Opin Lipidol 2020 31 4 182 186 32487819
  35. [42]Sarett SM Nelson CE Duvall CL Technologies for controlled, local delivery of siRNA J Control Release 2015 218 94 113 26476177 PMC4665980
  36. [44]Cordero A Santos-Gallego CG Facila L Estimation of the major cardiovascular events prevention with Inclisiran Atherosclerosis 2020 313 76 80 33032236
  37. [48]Wright RS Collins MG Stoekenbroek RM Robson R Wijngaard PLJ Landmesser U Leiter LA Kastelein JJP Ray KK Kallend D Effects of renal impairment on the pharmacokinetics, efficacy, and safety of inclisiran: an analysis of the ORION-7 and ORION-1 studies Mayo Clin Proc 2020 95 1 77 89 31630870
  38. [52]Goldberg AC Leiter LA Stroes ESG Baum SJ Hanselman JC Bloedon LAT Lalwani ND Patel PM Zhao X Duell PB 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 31714986 PMC6865290
  39. [53]Banach M Duell PB Gotto AM Jr Laufs U Leiter LA Mancini GBJ Ray KK Flaim JA Ye Z Catapano AL Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia JAMA Cardiol 2020 5 1124 PMC7330832 32609313
  40. [54]Ballantyne CM Laufs U Ray KK Leiter LA Bays HE Goldberg AC Stroes ESG MacDougall D Zhao X Catapano 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 2020 27 6 593 603 31357887 PMC7153222
  41. [55]Khan MU Khan MZ Munir MB Balla S Khan SU Meta-analysis of the safety and efficacy of bempedoic acid Am J Cardiol 2020 131 130 132 32711805
  42. [56]Ference BA Ray KK Catapano AL Ference TB Burgess S Neff DR Oliver-Williams C Wood AM Butterworth AS di Angelantonio E Danesh J Kastelein JJP Nicholls SJ Mendelian randomization study of ACLY and cardiovascular disease N Engl J Med 2019 380 11 1033 1042 30865797 PMC7612927
  43. [57]Gusarova V Alexa CA Wang Y Rafique A Kim JH Buckler D Mintah IJ Shihanian LM Cohen JC Hobbs HH Xin Y Valenzuela DM Murphy AJ Yancopoulos GD Gromada J ANGPTL3 blockade with a human monoclonal antibody reduces plasma lipids in dyslipidemic mice and monkeys J Lipid Res 2015 56 7 1308 1317 25964512 PMC4479335
  44. [58]Arca M D'Erasmo L Minicocci I Familial combined hypolipidemia: angiopoietin-like protein-3 deficiency Curr Opin Lipidol 2020 31 2 41 48 32022755
  45. [59]Dewey FE Gusarova V Dunbar RL O’Dushlaine C Schurmann C Gottesman O McCarthy S van Hout CV Bruse S Dansky HM Leader JB Murray MF Ritchie MD Kirchner HL Habegger L Lopez A Penn J Zhao A Shao W Stahl N Murphy AJ Hamon S Bouzelmat A Zhang R Shumel B Pordy R Gipe D Herman GA Sheu WHH Lee IT Liang KW Guo X Rotter JI Chen YDI Kraus WE Shah SH Damrauer S Small A Rader DJ Wulff AB Nordestgaard BG Tybjærg-Hansen A van den Hoek AM Princen HMG Ledbetter DH Carey DJ Overton JD Reid JG Sasiela WJ Banerjee P Shuldiner AR Borecki IB Teslovich TM Yancopoulos GD Mellis SJ Gromada J Baras A Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease N Engl J Med 2017 377 3 211 221 28538136 PMC5800308
  46. [60]Gaudet D Gipe DA Pordy R Ahmad Z Cuchel M Shah PK Chyu KY Sasiela WJ Chan KC Brisson D Khoury E Banerjee P Gusarova V Gromada J Stahl N Yancopoulos GD Hovingh GK ANGPTL3 inhibition in homozygous familial hypercholesterolemia N Engl J Med 2017 377 3 296 297 28723334
  47. [61]Raal FJ Rosenson RS Reeskamp LF Hovingh GK Kastelein JJP Rubba P Ali S Banerjee P Chan KC Gipe DA Khilla N Pordy R Weinreich DM Yancopoulos GD Zhang Y Gaudet D Evinacumab for homozygous familial hypercholesterolemia N Engl J Med 2020 383 8 711 720 32813947
  48. [63]Harada-Shiba M Ali S Gipe DA Gasparino E Son V Zhang Y Pordy R Catapano AL A randomized study investigating the safety, tolerability, and pharmacokinetics of evinacumab, an ANGPTL3 inhibitor, in healthy Japanese and Caucasian subjects Atherosclerosis 2020 314 33 40 33130482
  49. [64]Emerging Risk Factors C Erqou S Kaptoge S Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality JAMA 2009 302 4 412 423 19622820 PMC3272390
  50. [65]Saleheen D Haycock PC Zhao W Rasheed A Taleb A Imran A Abbas S Majeed F Akhtar S Qamar N Zaman KS Yaqoob Z Saghir T Rizvi SNH Memon A Mallick NH Ishaq M Rasheed SZ Memon FUR Mahmood K Ahmed N Frossard P Tsimikas S Witztum JL Marcovina S Sandhu M Rader DJ Danesh J Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis Lancet Diabetes Endocrinol 2017 5 7 524 533 28408323 PMC5483508
  51. [67]Greco MF, Sirtori CR, Corsini A, Ezhov M, Sampietro T, Ruscica M. Lipoprotein(a) lowering-from lipoprotein apheresis to antisense oligonucleotide approach. J Clin Med. 2020 Jul 3;9(7):2103. PMC7408876 32635396
  52. [68]Willeit P, Ridker PM, Nestel PJ, Simes J, Tonkin AM, Pedersen TR, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet. 2018;392(10155):1311–20. 30293769
  53. [69]Tsimikas S Gordts P Nora C Yeang C Witztum JL Statin therapy increases lipoprotein(a) levels Eur Heart J 2020 41 24 2275 2284 31111151
  54. [70]Ruscica M Greco MF Ferri N Corsini A Lipoprotein(a) and PCSK9 inhibition: clinical evidence Eur Heart J Suppl 2020 22 Suppl L L53 L56 33239979 PMC7673619
  55. [71]Szarek M Bittner VA Aylward P Baccara-Dinet M Bhatt DL Diaz R Fras Z Goodman SG Halvorsen S Harrington RA Jukema JW Moriarty PM Pordy R Ray KK Sinnaeve P Tsimikas S Vogel R White HD Zahger D Zeiher AM Steg PG Schwartz GG for the ODYSSEY OUTCOMES Investigators Lipoprotein(a) lowering by alirocumab reduces the total burden of cardiovascular events independent of low-density lipoprotein cholesterol lowering: ODYSSEY OUTCOMES trial Eur Heart J 2020 41 4245 4255 33051646 PMC7724642
  56. [72]Wilson DP Jacobson TA Jones PH Koschinsky ML McNeal CJ Nordestgaard BG Orringer CE Use of lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association J Clin Lipidol 2019 13 3 374 392 31147269
  57. [74]Schettler VJJ Neumann CL Peter C Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels Clin Res Cardiol Suppl 2019 14 Suppl 1 33 38 30838552
  58. [76]Koren M, Moriarty P, Neutel J, et al. Abstract 13951: Safety, tolerability and efficacy of singledose Amg 890, a novel Sirna targeting Lp(a), in healthy subjects and subjects with elevated Lp(a). Circulation. 2020;142:A13951.
  59. [77]Ferri N Corsini A Sirtori C Ruscica M PPAR-alpha agonists are still on the rise: an update on clinical and experimental findings Expert Opin Investig Drugs 2017 26 5 593 602 28343425
  60. [78]Dubois V Eeckhoute J Lefebvre P Staels B Distinct but complementary contributions of PPAR isotypes to energy homeostasis J Clin Invest 2017 127 4 1202 1214 28368286 PMC5373878
  61. [79]Botta M, Audano M, Sahebkar A, Sirtori CR, Mitro N, Ruscica M. PPAR agonists and metabolic syndrome: an established role? Int J Mol Sci. 2018 Apr 14;19(4):1197. PMC5979533 29662003
  62. [81]Preidis GA, Kim KH, Moore DD. Nutrientsensing nuclear receptors PPARα and FXR control liver energy balance. J Clin Invest. 2017 Apr 3;127(4):1193–201. PMC5373864 28287408
  63. [82]Kersten S Integrated physiology and systems biology of PPARalpha Mol Metab 2014 3 4 354 371 24944896 PMC4060217
  64. [83]Zandbergen F Plutzky J PPARalpha in atherosclerosis and inflammation Biochim Biophys Acta 2007 1771 8 972 982 17631413 PMC2083576
  65. [84]Sirtori CR Yamashita S Greco MF Corsini A Watts GF Ruscica M Recent advances in synthetic pharmacotherapies for dyslipidaemias Eur J Prev Cardiol 2020 27 15 1576 1596 31060364
  66. [86]Ishibashi S Arai H Yokote K Araki E Suganami H Yamashita S K-877 Study Group Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor alpha modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial J Clin Lipidol 2018 12 1 173 184 29203092
  67. [89]Sirtori CR Galli C Franceschini G Fraudulent (and non fraudulent) fatty acids for human health Eur J Clin Invest 1993 23 11 686 689 8307087
  68. [90]Calder PC Mechanisms of action of (n-3) fatty acids J Nutr 2012 142 3 592S 599S 22279140
  69. [91]Masters C Omega-3 fatty acids and the peroxisome Mol Cell Biochem 1996 165 2 83 93 8979256
  70. [92]Burke MF Burke FM Soffer DE Review of cardiometabolic effects of prescription omega-3 fatty acids Curr Atheroscler Rep 2017 19 12 60 29116404
  71. [93]Buoite Stella A, Gortan Cappellari G, Barazzoni R, Zanetti M: Update on the impact of omega 3 fatty acids on inflammation, insulin resistance and sarcopenia: a review. Int J Mol Sci. 2018 Jan 11;19(1):218. PMC5796167 29324650
  72. [96]Budoff MJ Bhatt DL Kinninger A Lakshmanan S Muhlestein JB le VT May HT Shaikh K Shekar C Roy SK Tayek J Nelson JR Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial Eur Heart J 2020 41 3925 3932 32860032 PMC7654934
  73. [99]Lakshmanan S Shekar C Kinninger A Dahal S Onuegbu A Cai AN Hamal S Birudaraju D Roy SK Nelson JR Budoff MJ Bhatt DL Comparison of mineral oil and non-mineral oil placebo on coronary plaque progression by coronary computed tomography angiography Cardiovasc Res 2020 116 3 479 482 31825484 PMC7031703
  74. [101]•• Gaudet D, Karwatowska-Prokopczuk E, Baum SJ, et al. Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia. Eur Heart J. 2020; In this phase 2 study, the antisense oligonucleotide Vupanorsen results in a favourable lipid/lipoprotein profile and provides a potential strategy for residual cardiovascular risk reduction. Eur Heart J. 2020;41(40):3936–45 PMC7750927 32860031
  75. [102]D'Erasmo L, Di Costanzo A, Gallo A, Bruckert E, Arca M. ApoCIII: A multifaceted protein in cardiometabolic disease. Metabolism. 2020 Dec;113:154395. 33058850
  76. [103]van Capelleveen JC Lee SR Verbeek R Kastelein JJP Wareham NJ Stroes ESG Hovingh GK Khaw KT Boekholdt SM Witztum JL Tsimikas S Relationship of lipoprotein-associated apolipoprotein C-III with lipid variables and coronary artery disease risk: the EPIC-Norfolk prospective population study J Clin Lipidol 2018 12 6 1493 1501 30249512 PMC6970616
  77. [104]Kanter JE Shao B Kramer F Barnhart S Shimizu-Albergine M Vaisar T Graham MJ Crooke RM Manuel CR Haeusler RA Mar D Bomsztyk K Hokanson JE Kinney GL Snell-Bergeon JK Heinecke JW Bornfeldt KE Increased apolipoprotein C3 drives cardiovascular risk in type 1 diabetes J Clin Invest 2019 129 10 4165 4179 31295146 PMC6763229
  78. [105]Barr SI Kottke BA Mao SJ Postprandial exchange of apolipoprotein C-III between plasma lipoproteins Am J Clin Nutr 1981 34 2 191 198 7211723
  79. [107]Taskinen MR Packard CJ Boren J Emerging evidence that ApoC-III inhibitors provide novel options to reduce the residual CVD Curr Atheroscler Rep 2019 21 8 27 31111320 PMC6527792
  80. [108]Khetarpal SA Zeng X Millar JS Vitali C Somasundara AVH Zanoni P Landro JA Barucci N Zavadoski WJ Sun Z de Haard H Toth IV Peloso GM Natarajan P Cuchel M Lund-Katz S Phillips MC Tall AR Kathiresan S DaSilva-Jardine P Yates NA Rader DJ A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels Nat Med 2017 23 9 1086 1094 28825717 PMC5669375
  81. [110]Witztum JL Gaudet D Freedman SD Alexander VJ Digenio A Williams KR Yang Q Hughes SG Geary RS Arca M Stroes ESG Bergeron J Soran H Civeira F Hemphill L Tsimikas S Blom DJ O’Dea L Bruckert E Volanesorsen and triglyceride levels in familial chylomicronemia syndrome N Engl J Med 2019 381 6 531 542 31390500
  82. [112]Fogacci F Norata GD Toth PP Arca M Cicero AFG Efficacy and safety of volanesorsen (ISIS 304801): the evidence from phase 2 and 3 clinical trials Curr Atheroscler Rep 2020 22 5 18 32458077
  83. [113]Alexander VJ Xia S Hurh E Hughes SG O’Dea L Geary RS Witztum JL Tsimikas S N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels Eur Heart J 2019 40 33 2785 2796 31329855 PMC6736334
  84. [114]Qamar A, Libby P, Bhatt DL. Targeting RNA to lower triglycerides: long strides from short molecules. Eur Heart J. 2019 Sep 1;40(33):2797–800. PMC6735893 31089714
  85. [115]Santos RD Stein EA Hovingh GK Blom DJ Soran H Watts GF López JAG Bray S Kurtz CE Hamer AW Raal FJ Long-term evolocumab in patients with familial hypercholesterolemia J Am Coll Cardiol 2020 75 6 565 574 32057369
  86. [116]Santos RD Ruzza A Hovingh GK Wiegman A Mach F Kurtz CE Hamer A Bridges I Bartuli A Bergeron J Szamosi T Santra S Stefanutti C Descamps OS Greber-Platzer S Luirink I Kastelein JJP Gaudet D Evolocumab in pediatric heterozygous familial hypercholesterolemia N Engl J Med 2020 383 14 1317 1327 32865373
  87. [117]Adam RC Mintah IJ Alexa-Braun CA Shihanian LM Lee JS Banerjee P Hamon SC Kim HI Cohen JC Hobbs HH van Hout C Gromada J Murphy AJ Yancopoulos GD Sleeman MW Gusarova V Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance J Lipid Res 2020 61 9 1271 1286 32646941 PMC7469887
  88. [118]Wu L Soundarapandian MM Castoreno AB Millar JS Rader DJ LDL-Cholesterol reduction by ANGPTL3 inhibition in mice is dependent on endothelial lipase Circ Res 2020 127 8 1112 1114 32808882 PMC10150441
  89. [119]Domanski MJ Tian X Wu CO Reis JP Dey AK Gu Y Zhao L Bae S Liu K Hasan AA Zimrin D Farkouh ME Hong CC Lloyd-Jones DM Fuster V Time course of LDL cholesterol exposure and cardiovascular disease event risk J Am Coll Cardiol 2020 76 13 1507 1516 32972526
  90. [120]•• Ray K, Molemans B, Schoonen W, et al. EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study. Eur J Prev Cardiol. 2020; In the context of lipid lowering approaches, there is a gap between clinical guidelines and clinical practice. In clinical care, there is the need of a greater utilization of non-statin lipid-lowering therapies in combination with statins for patients at highest risk. 33580789
  91. [121]Kam N Perera K Zomer E Liew D Ademi Z Inclisiran as adjunct lipid-lowering therapy for patients with cardiovascular disease: a cost-effectiveness analysis Pharmacoeconomics 2020 38 9 1007 1020 32789593
  92. [122]Koskinas KC, Gencer B, Nanchen D, et al. Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines. Eur J Prev Cardiol. 2020:2047487320940102. 33755142
  93. [123]Iitake C Masuda D Koseki M Yamashita S Marked effects of novel selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate in severe hypertriglyceridemia: preliminary report Cardiovasc Diabetol 2020 19 1 201 33246467 PMC7694943
  94. [124]Boden WE Bhatt DL Toth PP Ray KK Chapman MJ Luscher TF Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics Eur Heart J 2020 41 24 2304 2312 31872245 PMC7308541
  95. [125]Poppe K, Wells S, Jackson R, Doughty R, Kerr A. Predicting cardiovascular disease risk across the atherosclerotic disease continuum. Online ahead of print. Eur J Prev Cardiol. 2021 Jan 18;zwaa168. 33624049
  96. [126]Sharma G, Martin SS, Blumenthal RS. Effects of omega-3 fatty acids on major adverse cardiovascular events: what matters most: the drug, the dose, or the placebo? JAMA. 2020 Dec 8;324(22):2262–4. 33190148

Authors
Ruscica, M., Ferri, N., Santos, R. D., Sirtori, C. R., & Corsini, A.
Affiliations
  • University of Milan (IT)
  • University of Padua (IT)
  • Universidade de São Paulo (BR)
Corresponding author
  • Ruscica, Massimiliano
  • Corsini, Alberto
ORCID
Venue
Current Atherosclerosis Reports
Publisher
Springer Science and Business Media LLC
Published
2021-03-10
Volume
23
Issue
5
Pages
17-17
ISSN
  • 1523-3804 (ISSN-L)
  • 1534-6242
DOI
10.1007/s11883-021-00918-3
PMC
PMC7946696
OpenAlex
W3135240275
Cited by
73
References
126
Citations by year
2026: 6 · 2025: 10 · 2024: 12 · 2023: 14 · 2022: 23 · 2021: 8
FWCI
3.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Atherosclerosis Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
Università degli Studi di Milano
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
lipid-lowering drugs, hypercholesterolemia, hypertriglyceridemia, bempedoic acid, inclisiran, PCSK9 inhibition, statins, icosapent ethyl, pemafibrate, PPARα agonist, RNA therapeutics, lipoprotein(a), ANGPTL3, triglyceride-rich lipoproteins, cardiovascular risk reduction
MeSH terms
Proprotein Convertase 9, Anticholesteremic Agents, Humans, Hypercholesterolemia, Lipids, Cholesterol, LDL, Hypertriglyceridemia, Lipoprotein(a)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review