Skip to main content
SpringerLink
Log in

Beyond Statins: New Lipid Lowering Strategies to Reduce Cardiovascular Risk

  • Cardiovascular Disease and Stroke (P Perrone-Filardi and S. Agewall, Section Editors)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Statins are the first-line therapy in LDL-Cholesterol (LDL-C) reduction and its clinical use has contributed to significant prevention and treatment of atherosclerotic vascular disease. Yet, a significant proportion of patients remain at high risk. Recently, a number of new therapies have been developed to further lower LDL-C. These agents may provide clinical benefit on top of statin therapy in patients with high residual risk, severe hypercholesterolemia or as an alternative for patients who are intolerant to statins. We review four novel approaches based on the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein-B100 (apoB), Cholesteryl ester transport protein (CETP) and microsomal triglyceride transfer protein (MTP). ApoB and MTP inhibitors (Mipomersen and Lomitapide) are indicated only for homozygous familial hypercholesterolemia patients. The results of ongoing trials with CETP and PCSK9 inhibitors may warrant a wider employment in different categories of patients at high risk for cardiovascular disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Go AS, Mozaffariam D, Roger VL, on behalf of the American Heart Association Statistics Committee and Stroke Statistics subcommittee, et al. Heart disease and stroke statistics: 2013 update: a report from the American Heart Association. Circulation. 2013;127:e6–245.

    Article  PubMed  Google Scholar 

  2. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.

  3. Smith Jr SC, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124:2458–73.

    Article  PubMed  Google Scholar 

  4. Waters DD, Brotons C, Chiang CW, et al. Lipid treatment assessment project 2: a multinational survey to evaluate the proportion of patients achieving low-density lipoprotein cholesterol goals. Circulation. 2009;120:28–34.

    Article  CAS  PubMed  Google Scholar 

  5. The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.

    Article  Google Scholar 

  6. The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–74.

    Article  PubMed Central  Google Scholar 

  7. Cannon CP, Giugliano RP, Blazing MA, et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008;156:826–32.

    Article  CAS  PubMed  Google Scholar 

  8. Califf RM, Lokhnygina Y, Cannon CP, et al. An update on the IMProved reduction of outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design. Am Heart J. 2010;159:705–9.

    Article  PubMed  Google Scholar 

  9. Bertolini S, Pisciotta L, Rabacchi C, et al. Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Atherosclerosis. 2013;227(2):342–8.

    Article  CAS  PubMed  Google Scholar 

  10. Packard CJ, Demant T, Stewart JP, et al. Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. J Lipid Res. 2000;41:305–18.

    CAS  PubMed  Google Scholar 

  11. Elovson J, Chatterton JE, Bell GT, et al. Plasma very low density lipoproteins contain a single molecule of apolipoprotein B. J Lipid Res. 1998;29:1461–73.

    Google Scholar 

  12. Bennett CF, Swayze EE. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol. 2010;50:259–93.

    Article  CAS  PubMed  Google Scholar 

  13. Kurreck J. Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem. 2003;270:1628–44.

    Article  CAS  PubMed  Google Scholar 

  14. Thomas T, Ginsberg H. Targeting ApoB as a therapeutic approach for the treatment of dyslipidemia: the potential role of mipomersen. Clin Lipidol. 2010;5:457–64.

    Article  CAS  Google Scholar 

  15. Kastelein JJ, Wedel MK, Baker BF, et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006;114(16):1729–35.

    Article  CAS  PubMed  Google Scholar 

  16. Akdim F, Stroes ES, Sijbrands EJ, et al. Efficacy and safety of mipomersen, an antisense inhibitor of apolipoprotein B, in hypercholesterolemic subjects receiving stable statin therapy. J Am Coll Cardiol. 2010;55:1611–8.

    Article  CAS  PubMed  Google Scholar 

  17. Visser ME, Akdim F, Tribble DL, et al. Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J Lipid Res. 2010;51:1057–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Stein E, Dufour R, Gagne C, et al. A randomized, double-blind, placebo-controlled study to assess efficacy and safety of mipomersen as add-on therapy in heterozygous familial hypercholesterolemia patients with coronary artery disease. Eur Heart J. 2010;31:S898.

    Google Scholar 

  19. Tardif JC, Mcgowan M, Ceska R, et al. Apolipoprotein B synthesis inhibition by mipomersen reduces LDL-C when added to maximally tolerated lipid-lowering medication in patients with severe heterozygous hypercholesterolemia. J Am Coll Cardiol. 2011;57:E492.

    Article  Google Scholar 

  20. Visser ME, Wagener G, Baker BF, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2012;33(9):1142–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998–1006. This paper demonstrated that mipomersen is effective in reducing LDL-C levels in homozygous familial Hypercholesterolemia.

    Article  CAS  PubMed  Google Scholar 

  22. Thomas GS, Cromwell WC, Ali S, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2013;62(23):2178–84. First phase III study testing mipomersen in patients at high cardiovascular risk.

    Article  CAS  PubMed  Google Scholar 

  23. Yu RZ, Geary RS, Flaim JD, et al. Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a2’-O-methoxyethyl modified antisense oligonucleotide targeting apolipoproteinB-100 messenger RNA, with simvastatin and ezetimibe. Clin Pharmacokinet. 2009;48:39–50.

    Article  CAS  PubMed  Google Scholar 

  24. Tarugi P, Averna M, Di Leo E, et al. Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis. 2007;195:e19–27.

    Article  CAS  PubMed  Google Scholar 

  25. Cefalù AB, Pirruccello JP, Noto D, et al. A novel APOB mutation identified by exome sequencing cosegregates with steatosis, liver cancer, and hypocholesterolemia. Arterioscler Thromb Vasc Biol. 2013;33(8):2021–5.

    Article  PubMed  Google Scholar 

  26. Seidah NG, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003;100:928–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Lambert G, Sjouke B, Choque B, et al. The PCSK9 decade. J Lipid Res. 2012;53(12):2515–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Abifadel M, Varret M, Rabes JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–6.

    Article  CAS  PubMed  Google Scholar 

  29. Fasano T, Cefalù AB, Di Leo E, et al. A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol. 2007;27(3):677–81.

    Article  CAS  PubMed  Google Scholar 

  30. Cohen JC, Boerwinkle E, Mosley Jr TH, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264–72.

    Article  CAS  PubMed  Google Scholar 

  31. Zhao Z, Tuakli-Wosornu Y, Lagace TA, et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet. 2006;79(3):514–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Dubuc G, Chamberland A, Wassef H, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2004;24:1454–9.

    Article  CAS  PubMed  Google Scholar 

  33. Rashid S, Curtis DE, Garuti R, et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking PCSK9. Proc Natl Acad Sci U S A. 2005;102:5374–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Catapano AL, Papadopoulos N. The safety of therapeutic monoclonal antibodies: Implications for cardiovascular disease and targeting thePCSK9 pathway. Atherosclerosis. 2013;228:18–28. This is a comprehensive review on PCSK9 function and therapeutic opportunities.

    Article  CAS  PubMed  Google Scholar 

  35. Chan JC, Piper DE, Cao Q, et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and non human primates. Proc Natl Acad Sci U S A. 2009;106:9820–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Ni YG, Di MS, Condra JH, et al. A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo. J Lipid Res. 2011;52:78–86.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. 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):1108–18.

    Article  CAS  PubMed  Google Scholar 

  38. McKenney JM, Koren MJ, Kereiakes DJ, et al. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59(25):2344–53.

    Article  CAS  PubMed  Google Scholar 

  39. Stein EA, Gipe D, Bergeron J, et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet. 2012;380(9836):29–36.

    Article  CAS  PubMed  Google Scholar 

  40. Roth EM, McKenney JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012;367(20):1891–900.

    Article  CAS  PubMed  Google Scholar 

  41. Dias CS, Shaywitz AJ, Wasserman SM, et al. Effects of AMG 145 on low density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J Am Coll Cardiol. 2012;60(19):1888–98.

    Article  CAS  PubMed  Google Scholar 

  42. Koren MJ, Scott R, Kim JB, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012;380(9858):1995–2006.

    Article  CAS  PubMed  Google Scholar 

  43. Raal F, Scott R, Somaratne R, et al. Low-density lipoprotein cholesterol lowering effects of AMG145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012;126(20):2408–17.

    Article  CAS  PubMed  Google Scholar 

  44. Giugliano RP, Desai NR, Kohli P, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012;380(9858):2007–17.

    Article  CAS  PubMed  Google Scholar 

  45. Raal FJ, Giugliano RP, Sabatine MS, Koren MJ, Langslet G, Bays H, et al. Reduction in lipoprotein(a) with the PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of over 1300 patients in 4 phase 2 trials. J Am Coll Cardiol. 2014. doi:10.1016/j.jacc.2014.01.006.

    PubMed  Google Scholar 

  46. Stein EA, Honarpour N, Wasserman SM, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013;128(19):2113–20.

    Article  CAS  PubMed  Google Scholar 

  47. Shan L, Pang L, Zhang R, et al. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun. 2008;375:69–73.

    Article  CAS  PubMed  Google Scholar 

  48. Mc Nutt MC, Kwon HJ, Chen C, et al. Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells. J Biol Chem. 2009;284:10561–70.

    Article  CAS  Google Scholar 

  49. Schroeder CI, Swedberg JE, Withka JM, et al. Design and synthesis of truncated EGF-A peptides that restore LDL-R recycling in the presence of PCSK9 in vitro. Chem Biol. 2014. doi:10.1016/j.chembiol.2013.11.014.

    PubMed  Google Scholar 

  50. Zhang Y, Eigenbrot C, Zhou L, et al. Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. J Biol Chem. 2014;289(2):942–55.

    Article  CAS  PubMed  Google Scholar 

  51. Du F, Hui Y, Zhang M, et al. Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem. 2011;286:43054–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Graham MJ, Lemonidis KM, Whipple CP, et al. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res. 2007;48:763–7.

    Article  CAS  PubMed  Google Scholar 

  53. Gupta N, Fisker N, Asselin MC, et al. A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PLoS One. 2010;5:10682. doi:10.1371/journal.pone.0010682.

    Article  Google Scholar 

  54. Lindholm MW, Elmen J, Fisker N, et al. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates. Mol Ther. 2012;20:376–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Barter P. HDL-C: role as a risk modifier. Atheroscler Suppl. 2011;12(3):267–70. This is a review of evidence of the role of HDL-C on cardiovascular risk.

    Article  CAS  PubMed  Google Scholar 

  56. Klerkx AH, El Harchaoui K, van der Steeg WA, et al. Cholesteryl ester transfer protein (CETP) inhibition beyond raising high-density lipoprotein cholesterol levels: pathways by which modulation of CETP activity may alter atherogenesis. Arterioscler Thromb Vasc Biol. 2006;26(4):706–15.

    Article  CAS  PubMed  Google Scholar 

  57. Brown ML, Inazu A, Hesler CB, et al. Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins. Nature. 1989;342(6248):448–51.

    Article  CAS  PubMed  Google Scholar 

  58. Kurasawa T, Yokoyama S, Miyake, et al. Rate of cholesteryl ester transfer between high and low density lipoproteins in human serum and a case with decreased transfer rate in association with hyperalphalipoproteinemia. J Biochem. 1985;98:1499–508.

    CAS  PubMed  Google Scholar 

  59. Cefalù AB, Noto D, Magnolo L, et al. Novel mutations of CETP gene in Italian subjects with hyperalphalipoproteinemia. Atherosclerosis. 2009;204(1):202–7.

    Article  PubMed  Google Scholar 

  60. Zhong S, Sharp DS, Grove JS, et al. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest. 1996;97:2917–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350(15):1505–15.

    Article  CAS  PubMed  Google Scholar 

  62. Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22.

    Article  CAS  PubMed  Google Scholar 

  63. Clerc RG, Stauffer A, Weibel F, et al. Mechanisms underlying off-target effects of the cholesteryl ester transfer protein inhibitor torcetrapib involve L-type calcium channels. J Hypertens. 2010;28(8):1676–86.

    Article  CAS  PubMed  Google Scholar 

  64. Nissen SE, Tardif JC, Nicholls SJ, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007;356(13):1304–16.

    Article  CAS  PubMed  Google Scholar 

  65. Stein EA, Roth EM, Rhyne JM, et al. Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial. Eur Heart J. 2010;31(4):480–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22):2089–99.

    Article  CAS  PubMed  Google Scholar 

  67. Fayad ZA, Mani V, Woodward M, et al. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. 2011;378(9802):1547–59.

    Article  CAS  PubMed  Google Scholar 

  68. Lüscher TF, Taddei S, Kaski JC, et al. Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial. Eur Heart J. 2012;33(7):857–65.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Cannon CP, Shah S, Dansky HM, et al. Determining the Efficacy and Tolerability Investigators. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010;363(25):2406–15.

    Article  CAS  PubMed  Google Scholar 

  70. Gotto Jr AM, Cannon CP, Li XS, et al. Evaluation of lipids, drug concentration, and safety parameters following cessation of treatment with the cholesteryl ester transfer protein inhibitor anacetrapib in patients with or at high risk for coronary heart disease. Am J Cardiol. 2014;113(1):76–83. This paper confirms that anacetrapib is effective in increasing HDL-C and safe for patients at high-risk.

    Article  CAS  PubMed  Google Scholar 

  71. ClinicalTrials.gov. 2013. REVEAL: Randomized Evaluation of the Effects of Anacetrapib through Lipid- Modification. http://clinicaltrials.gov/show/NCT01252953.

  72. Nicholls SJ, Brewer HB, Kastelein JJ, et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA. 2011;306(19):2099–109.

    Article  CAS  PubMed  Google Scholar 

  73. ClinicalTrials.gov. 2013. ACCELERATE: A Study of Evacetrapib in High-Risk Vascular Disease. http://www.clinicaltrials.gov/ct2/show/NCT01687998

  74. Raabe M, Véniant MM, Sullivan MA, et al. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest. 1999;103(9):1287–98.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Gordon DA, Jamil H. Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly. Biochim Biophys Acta. 2000;1486(1):72–83.

    Article  CAS  PubMed  Google Scholar 

  76. Samaha FF, McKenney J, Bloedon LT, et al. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2008;5(8):497–505.

    Article  CAS  PubMed  Google Scholar 

  77. Benn M, Watts GF, Tybjaerg-Hansen A, et al. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012;97(11):3956–64.

    Article  CAS  PubMed  Google Scholar 

  78. Nordestgaard BG, Chapman MJ, Humphries SE, for the European Atherosclerosis Society Consensus Panel, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–90a.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med. 2007;356(2):148–56.

    Article  CAS  PubMed  Google Scholar 

  80. Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40–6. This phase III trial demonstrates safety and efficacy of lomitapide in homozygous FH patients.

    Article  CAS  PubMed  Google Scholar 

  81. Aegerion Pharmaceuticals Inc. US prescribing information for JuxtapidTM (lomitapide). 2013. http://www.juxtapid.com/_pdf/Prescribing_Information.pdf.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Maurizio Averna, Angelo B. Cefalù, and Davide Noto have served as clinical investigators in several hypolipidemic drug trials for Aegerion Merck, Pfizer, Sanofi, and Astra Zeneca. MR Averna is a member of Aegerion Europe and Italy Advisory Boards. The authors have no other relevant affiliations and financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Dipartimento Biomedico di Medicina Interna e Specialistica, Università degli Studi di Palermo, Palermo, Italy

    Davide Noto, Angelo B. Cefalù & Maurizio R. Averna

  2. Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.Mi.S), Policlinico “Paolo Giaccone”, University of Palermo, Via del Vespro 141, 90127, Palermo, Italy

    Davide Noto, Angelo B. Cefalù & Maurizio R. Averna

Authors
  1. Davide Noto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angelo B. Cefalù
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maurizio R. Averna
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maurizio R. Averna.

Additional information

This article is part of the Topical Collection on Cardiovascular Disease and Stroke

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noto, D., Cefalù, A.B. & Averna, M.R. Beyond Statins: New Lipid Lowering Strategies to Reduce Cardiovascular Risk. Curr Atheroscler Rep 16, 414 (2014). https://doi.org/10.1007/s11883-014-0414-4

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-014-0414-4

Keywords

Search

Navigation