616
Views
33
CrossRef citations to date
0
Altmetric
Review

Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data

, ORCID Icon & ORCID Icon
Pages 611-621 | Received 16 Feb 2019, Accepted 15 May 2019, Published online: 29 May 2019

References

  • Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–e322.
  • Ference BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631–2639.
  • Baigent C, Blackwell L, Emberson J, et al.; Collaboration Cholesterol Treatment Trialists. 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;376:1670–1681.
  • Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation. 2004;110:227–239.
  • 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.
  • Lemstra M, Blackburn D, Crawley A, et al. Proportion and risk indicators of nonadherence to statin therapy: a meta-analysis. Can J Cardiol. 2012;28:574–580.
  • Wei MY, Ito MK, Cohen JD, et al. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J Clin Lipidol. 2013;7(5):472–483.
  • Banach M, Rizzo M, Toth PP, et al. Statin intolerance – an attempt at a unified definition. Position paper from an international lipid expert panel. Expert Opin Drug Saf. 2015;14(6):935–955.
  • Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy - European atherosclerosis society consensus panel statement on assessment. Aetiology and management. Eur Heart J. 2015;36(17):1012–1022.
  • Rosenson RS, Baker S, Banach M, et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70(10):1290–1301.
  • Rajpathak SN, Kumbhani DJ, Crandall J, et al. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32:1924–1929.
  • Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–742.
  • Hsia SH, Desnoyers ML, Lee ML. Differences in cholesterol management among states in relation to health insurance and race/ethnicity across the United States. J Clin Lipidol. 2013;7(6):675–682.
  • Banach M, Stulc T, Dent R, et al. Statin non-adherence and residual cardiovascular risk: there is need for substantial improvement. Int J Cardiol. 2016;225:184–196.
  • Nielsen SF, Nordestgaard BG. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study. Eur Heart J. 2016;37(11):908–916.
  • Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–2397.
  • Zhan S, Tang M, Liu F, et al. Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events. Cochrane Database Syst Rev. 2018;11:CD012502
  • Wang D, Liu B, Tao W, et al. Fibrates for secondary prevention of cardiovascular disease and stroke. Cochrane Database Syst Rev. 2015;10:CD009580
  • Cicero AF, Landolfo M, Ventura F, et al. Current pharmacotherapeutic options for primary dyslipidemia in adults. Exp Opin Pharmacother 2019:1–12. Epub ahead of print.
  • 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):2109–2122.
  • Cicero AF, Tartagni E, Ertek S. Emerging drugs for the treatment of hypercholesterolemia. Expert Opin Drug Saf. 2014;13(8):1023–1030.
  • Zhang L, Song K, Zhu M, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism, atherosclerosis and ischemic stroke. Int J Neurosci. 2016;126(6):675–680.
  • Maxwell KN, Breslow JL. Adenoviral mediated expression of PCSK9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci USA. 2004;101:7100–7105.
  • Kasichyanula S, Grover A, Emery MG, et al. Clinical pharmacokinetics and pharmacodynamics of evolocumab, a PCSK9 inhibitor. Clin Pharmacokinet. 2018;57(7):769–779.
  • Ridker PM, Tardif J, Amarenco P, et al. SPIRE Investigators Lipid-lowering variability and antidrug-antibody formation with bococizumab. N Engl J Med. 2017;376(16):1517–1526.
  • Ridker PM, Revkin J, Amarenco R, et al. SPIRE cardiovascular outcome investigators cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376(16):1527–1539.
  • Zhao H, Xiang B. Discontinued cardiovascular drugs in 2013 and 2014. Expert Opin Invest Drugs. 2015;24(8):1083–1092.
  • Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J. 2015;169(6):906–915.
  • Marks D, Thorogood M, Neil HA, et al. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003;168(1):1–14.
  • Austin MA, Hutter CM, Zimmern RL, et al. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004;160(5):407–420.
  • Shah P, Glueck CJ, Goldenberg N. Efficacy, safety, low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study. Lipids Health Dis. 2017;16:19.
  • Sabatine MS, Giugliano RP, Wiviott SD, et al.; for the Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372(16):1500–1509.
  • Chan JC, Piper DE, Cao Q, et al. A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA. 2009;106:9820–9825.
  • 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;380:1995–2006.
  • Koren MJ, Lundqvist P, Bolognese M, et al. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014;63:2531–2540.
  • 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;380:2007–2017.
  • Robinson JG, Nedergaard BS, Rogers WJ, et al. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. Jama. 2014;311:1870–1882.
  • Raal F, Scott R, Somaratne R, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, 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;126:2408–2417.
  • Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2014;385(9965):331–340.
  • Toth PP, Descamps P, Genest J, et al. Pooled Safety Analysis of evolocumab in over 6,000 patients from double-blind and open-label extension studies. Circulation. 2017;135(19):1819–1831.
  • Cheng C, Sun S, Zhou Y, et al. Efficacy and safety of different doses of evolocumab in reducing low-density lipoprotein cholesterol levels: a meta-analysis. Biomed Rep. 2016;5(5):541–547.
  • Koren MJ, Sabatine MS, Giugliano RP, et al. Long-term low-density lipoprotein cholesterol–lowering efficacy, persistence, and safety of evolocumab in treatment of hypercholesterolemia. results up to 4 years from the open-label OSLER-1 extension study. JAMA Cardiol. 2017;2(6):598–607.
  • 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.
  • Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370(19):1809–1819.
  • Stroes E, Colquhoun D, Sullivan D, et al. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014;63(23):2541–2548.
  • 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.
  • Sabatine MS, Giugliano RP, Keech AC, et al. FOURIER steering committee and investigators evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Ned. 2017;376(18):1713–1722.
  • Mannarino MR, Sahebkar A, Biankoni V, et al. PCSK9 and neurocognitive function: should it be still an issue after FOURIER and EBBINGHAUS results? J Clin Lipidol. 2018;12(5):1123–1132.
  • Giugliano RP, Mach F, Zavitz K, et al. EBBINGHAUS investigators cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377(7):633–643.
  • Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk trial. Am Heart J. 2016;173:94–101.
  • Toth PP, Descamps O, Genest J, et al. A pooled safety analysis of over 6000 patients from double-blind and open-label extension studies with evolocumab. In: Proceedings of the Scientific Sessions of the American College of Cardiology. Chicago, IL: ACC, 2016.
  • Blom DJ, Koren MJ, Roth E, et al. Evaluation of the efficacy, safety, and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome. Diabetes Obes Metab. 2017;19:98–107.
  • Harding FA, Stickler MM, Razo J, et al. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010;2(3):256–265.
  • Gibbs JP, Slatter JG, Egbuna O, et al. Evaluation of evolocumab (AMG 145), a fully human anti-PCSK9 IgG2 monoclonal antibody, in subjects with hepatic impairment. J Clin Pharmacol. 2017;57:513–523.
  • Lee E, Gibbs J, Wasserman SM, et al. Pharmacokinetics and pharmacodynamics of evolocumab in patients with renal impairment. Eur Heart J. 2016;37(Suppl):343.
  • Blom DJ, Djedjos CS, Monsalvo ML, et al. Effects of evolocumab on vitamin e and steroid hormone levels: results from the 52-week, phase 3, double-blind, randomized, placebo-controlled DESCARTES study. Circ Res. 2015;117(8):731–741.
  • 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.
  • Roth EM, Taskinen MR, Ginsberg HN, et al. Monotherapy with the PCSK9 inhibitor alirocumabvs. ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized phase 3 trial. Int J Cardiol. 2014;176:55–61.
  • Bays H, Gaudet D, Weiss R, et al. Alirocumab as add-on to atorvastatin vs other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab. 2015;100:3140–3148.
  • Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489–1499.
  • Robinson JG, Colhoun HM, Bays HE, et al. Efficacy and safety of alirocumab as add-on therapy in high–cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014;37(10):597–604.
  • Praluent (alirocumab) injection [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US; Tarrytown, NY: Regeneron Pharmaceuticals; 2015 Oct. [cited 2019 May 25]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125559s002lbl.pdf 
  • Leiter LA, Müller-Wieland D, Baccara-Dinet MT, et al. Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 phase III ODYSSEY clinical trials. Diabet Med. 2018;35(1):121–130.
  • Farnier M, Jones P, Severance R, et al. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: the ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016;244:138–146.
  • Farnier M, Hovingh JK, Langslet G, et al. Long-term safety and efficacy of alirocumab in patients with heterozygous familial hypercholesterolemia: an open-label extension of the ODYSSEY program. Atherosclerosis. 2018;278:307–314.
  • Robinson JG, Rosenson RS, Farnier M, et al. Safety of very low low-density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials. J Am Coll Cardiol. 2017;69(5):471–482.
  • Hassan M. OSLER and ODYSSEY LONG TERM: PCSK9 inhibitors on the right track of reducing cardiovascular events. Glob Cardiol Sci Pract. 2015;2015(2):20.
  • Taskinen MR, Del Prato S, Bujas-Bobanovich M, et al. Efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus with or without mixed dyslipidaemia: analysis of the ODYSSEY LONG TERM trial. Atherosclerosis. 2018;276:124–130.
  • Ganda OP, Plutzky J, Sanganalmath SK, et al. Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials. Diabetes Obes Metab. 2018;20(10):2389–2398.
  • Leiter LA, Cariou B, Müller-Wieland D, et al. Efficacy and safety of alirocumab in insulin‐treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: the ODYSSEY DM‐INSULIN randomized trial. Diabetes Obes Metab. 2017;19(12):1781–1792.
  • Leiter LA, Tinahones FJ, Karalis DG, et al. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018;35(12):1742–1751.
  • Roth EM, Moriarty PM, Bergeron J, et al. A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis. 2016;254:254–262.
  • Stroes E, Guyton JR, Lepor N, et al. Efficacy and safety of alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study. J Am Heart Assoc. 2016;5(9):e003421.
  • Vallejo-Vaz A, Ginsberg HN, Davidson MH, et al. Lower on‐treatment low‐density lipoprotein cholesterol and major adverse cardiovascular events in women and men: pooled analysis of 10 ODYSSEY phase 3 alirocumab trials. J Am Heart Assoc. 2018;7(18):e009221.
  • Toth PP, Dwyer JP, Cannon CP, et al. Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease. Kidney Int. 2018;93(6):1397–1408.
  • Benedict PA, Abdou RM, Dion GR, et al. Association of alirocumab therapy with inflammatory lesions of the vocal folds: A case report. Laryngoscope. 2017;127(7):1652–1654.
  • Jhavery KD, Barta VS, Pullman J. Praluent (Alirocumab)-induced renal injury. J Pharm Pract. 2017;30(1):7–8.
  • Rosenson RS, Larrey D, Waters DD, et al. RE: praluent (Alirocumab)-induced renal injury. J Pharm Pract. 2018;31(2):138–139.
  • Kosmas CE, Estrella AM, Sourlas A, et al. Inclisiran: a new promising agent in the management of hypercholesterolemia. Diseases. 2018;6(3):63.
  • Ciccarelli G, D’Elia S, De Paulis M, et al. Lipid target in very high-risk cardiovascular patients: lesson from PCSK9 monoclonal antibodies. Diseases. 2018;6:22.
  • Bandyopadhyay D, Hajra A, Ashish K, et al. New hope for hyperlipidemia management: inclisiran. J Cardiol. 2018;71:523–524.
  • Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: A randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014;383:60–68.
  • Fitzgerald K, White S, Borodovsky A, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med. 2017;376:41–51.
  • Ray KK, Stoekenbroek RM, Kallend D, et al. Effect of an siRNA therapeutic targeting PCSK9 on atherogenic lipoproteins. Circulation. 2018;138:1304–1316.
  • Ray KK, Lansmesser 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.
  • Fogacci F, Ferri N, Toth P, et al. Efficacy and safety of mipomersen: a systematic review and meta-analysis of randomized clinical trials. Drugs. 2019;79(7):751–766.
  • Geary RS, Baker BF, Crooke ST. Clinical and preclinical pharmacokinetics and pharmacodynamics of mipomersen (Kynamro®): a second-generation antisense oligonucleotide inhibitor of apolipoprotein B. Clin Pharmacokinet. 2015;54:133–146.
  • Ricotta DN, Frishman W. Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia. Cardiol Rev. 2012;20:90–95.
  • Kynamro [Internet]. Genzyme Corporation: KYNAMRO® (mipomersen sodium) Injection Prescribing Information. 2013 [cited 2019 Jan 20]. Available from: http://www.kynamro.com/~/media/Kynamro/Files/KYNAMRO-PI.pdf
  • 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 randomized, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998–1006.
  • Akdim F, Visser ME, Tribble DL, et al. Effect of mipomersen, an apolipoprotein B inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol. 2010;105:1413–1419.
  • Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation. 2012;126:2283–2292.
  • McGowan MP, Tardif JC, Ceska R, et al. Randomized, placebo-controlled mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS One. 2012;7:e49006.
  • 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;62:2178–2184.
  • Dixon DL, Sisson EM, Butler M, et al. Lomitapide and mipomersen: novel lipid-lowering agents for the management of familial hypercholesterolemia. J Cardiovasc Nurs. 2014;29(5):E7–E12.
  • 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;33:1142–1149.
  • European Medicines Agency. Kynamro [Internet]. [cited 2019 Mar 29]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/kynamro
  • Hashemi N, Odze RD, McGowan MP, et al. Liver histology during mipomersen therapy for severe hypercholesterolemia. J Clin Lipidol. 2014;8(6):606–611.
  • Santos RD, Duell PB, East C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015;36(9):566-575.
  • Santos RD, Duell PB, East C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015;36(9):566–575.
  • Li Z, Yu R, Hard M, et al. The second generation antisense oligonucleotide (ASO) mipomersen does not prolong QT interval in a thorough QT/QTC study in healthy subjects. Clin Pharm Ther. 2014;95:S23.
  • Yu RZ, Geary RS, Flaim JD, et al. Lack of pharmacokinetic interaction of mipomersen sodium (ISIS 301012), a 2′-O-methoxyethyl modified antisense oligonucleotide targeting apolipoprotein B-100 messenger RNA, with simvastatin and ezetimibe. Clin Pharmacokinet. 2009;48:39–50.
  • Raal FJ, Braamskamp MJ, Selvey SL, et al. Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia. J Clin Lipidol. 2016;10(4):860–869.
  • Reiner Z. Triglyceride-rich lipoproteins and novel targets for anti-atherosclerotic therapy. Korean Circ J. 2018;48(12):1097–1119.
  • Gaudet D, Alexander VJ, Baker BF, et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. N Engl J Med. 2015;373:438–447.
  • Fogacci F, Cicero AF. Gene targeting for chylomicronemia syndrome: the brave new world. Atherosclerosis. 2018;269:254–255.
  • Moulin P, Dufour R, Averna M, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018;275:265–272.
  • Gaudet D, Digenio A, Alexander VJ, et al. The approach study: a randomized, double-blind, placebo-controlled, phase 3 study of volanesorsen administered subcutaneously to patients with familial chylomicronemia syndrome (FCS). J Clin Lipidol. 2017;11(3):814–815.
  • Gouni-Berthold I, Alexander V, Digenio A, et al. Apolipoprotein C-III inhibition with volanesorsen in patients with hypertrygliceridemia (COMPASS): a randomized, double-blind, placebo-controlled study. J Clin Lipidol. 2017;11(3):794–795.
  • Fierce Biotech [Internet]. FDA nixes Akcea’s volanesorsen despite favourable AdComm. Frammingham, MA, USA: Questex. [cited 2019 Mar 29]. Available from: https://www.fiercebiotech.com/biotech/fda-nixes-akcea-s-volanesorsen-despite-favorable-adcomm
  • Yu RZ, Graham MJ, Post N, et al. Disposition and pharmacology of a GalNAc3-conjugated ASO targeting human lipoprotein (a) in mice. Mol Ther Nucleic Acids. 2016;5(5):e317.
  • Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. Jama. 2009;302:412–423.
  • Erqou S, Thompson A, Di Angelantonio E, et al. Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. J Am Coll Cardiol. 2010;55:2160–2167.
  • Springer [Internet]. TQJ 230. Switzerland: Adis International Ltd.; 2019 [cited 2019 Apr 4]. Available from: https://adisinsight.springer.com/drugs/800042283
  • Clinicaltrials.gov. [Internet]. Phase 2 study of ISIS 681257 (AKCEA-APO(a)-LRx) in patients with hyperlipoproteinemia(a) and cardiovascular disease. Bethesda, USA: NIH; 2017 [Cited 2019 Jan 20]. Available from: https://clinicaltrials.gov/ct2/show/NCT03070782
  • Akcea Therapeutics, Inc. [Internet]. Washington (DC): annual report pursuant to section 13 or 15(d) of the securities exchange act of 1934. Cambridge, MA, USA. [cited 2019 Jan 20]. Available from: https://ir.akceatx.com/static-files/b8410a6e-fe4f-4440-b9cd-9fcd4b886204
  • Dewey FE, Gusarova V, Dunbar RL, et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. N Engl J Med. 2017;377:211–221.
  • Gaudet D, Gipe DA, Pordy R, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. N Engl J Med. 2017;377:296–297.
  • Graham MJ, Lee RG, Brandt TA, et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. N Engl J Med. 2017;377:222–232.
  • Banach M, Mikhailidis DP. Statin intolerance: some practical hints. Cardiol Clin. 2018;36(2):225–231.
  • Banach M, Penson PE. What have we learned about lipids and cardiovascular risk from PCSK9 inhibitor outcome trials: ODYSSEY and FOURIER? Cardiovasc Res. 2019;115(3):e26–e31.
  • Banach M, Rizzo M, Nikolic D, et al. Intensive LDL-cholesterol lowering therapy and neurocognitive function. Pharmacol Ther. 2017;170:181–191.
  • [cited 2018 May 14]. Available from: https://clinicaltrials.gov/ct2/show/NCT03872401.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.