Emerging biologic therapies for hypercholesterolaemia

References

• The top 10 causes of death WHO factsheet. [cited 2016 November 23]. Available from: http://www.who.int/mediacentre/factsheets/fs310/en/
   Google Scholar
• Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3:e442.
   PubMed Web of Science ®Google Scholar
• Stone NJ, Robinson JG, Lichtenstein AH, et al. ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1–S45.
   PubMed Web of Science ®Google Scholar
• Piepoli MF, Hoes AW, Agewall S, et al. European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;2016(37):2315–2381.
   Web of Science ®Google Scholar
• Cicero AF, Colletti A. Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: the available clinical data. Phytomedicine. 2016;23:1113–1118.
   PubMed Web of Science ®Google Scholar
• Sampson UK, Fazio S, Linton MF. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep. 2012;14:1–10.
   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;372:2387–2397.
   PubMed Web of Science ®Google Scholar
• Ridker PM. LDL cholesterol: controversies and future therapeutic directions. Lancet. 2014;384:607–617.
   PubMed Web of Science ®Google Scholar
• Jones PH, Nair R, Thakker KM. Prevalence of dyslipidemia and lipid goal attainment in statin-treated subjects from 3 data sources: a retrospective analysis. J Am Heart Assoc. 2012;1:e001800.
   PubMed Web of Science ®Google Scholar
• Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158:526–534.
   PubMed Web of Science ®Google Scholar
• Blom DJ, Dent R, Castro RC, et al. PCSK9 inhibition in the management of hyperlipidemia: focus on evolocumab. Vasc Health Risk Manag. 2016;12:185–197.
   PubMed Web of Science ®Google Scholar
• Turner RM, Yin P, Hanson A, et al. Investigating the prevalence, predictors, and prognosis of suboptimal statin use early after a non-ST elevation acute coronary syndrome. J Clin Lipidol. 2017;11:204–214.
   PubMed Web of Science ®Google Scholar
• Ahn CH, Choi SH. New drugs for treating dyslipidemia: beyond statins. Diabetes Metab J. 2015;39:87–94.
   PubMed Web of Science ®Google Scholar
• Farnier M. PCSK9: from discovery to therapeutic applications. Arch Cardiovasc Dis. 2014;107:58–66.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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 USA. 2003;100:928–933.
   PubMed Web of Science ®Google Scholar
• Abifadel M, Varret M, Rabès JP, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154–156. .
   PubMed Web of Science ®Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH Jr, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264–1272.
   PubMed Web of Science ®Google Scholar
• Marais DA, Blom DJ, Petrides F, et al. Proprotein convertase subtilisin/kexin type 9 inhibition. Curr Opin Lipidol. 2012;23:511–517.
   PubMed Web of Science ®Google Scholar
• Sible AM, Nawarskas JJ, Anderson JR. PCSK9 inhibitors: an innovative approach to treating hyperlipidemia. Cardiol Rev. 2016;24:141–152.
   PubMed Web of Science ®Google Scholar
• Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431–438.
   PubMed Web of Science ®Google Scholar
• Ito MK, Santos RD. PCSK9 inhibition with monoclonal antibodies – modern management of hypercholesterolemia. J Clin Pharmacol. 2017;57:7–32.
   PubMed Web of Science ®Google Scholar
• Liang H, Chaparro-Riggers J, Strop P, et al. Proprotein convertase substilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates. J Pharmacol Exp Ther. 2012;340:228–236.
   PubMed Web of Science ®Google Scholar
• Farnier M. PCSK9 inhibitors. Curr Opin Lipidol. 2013;24:251–258.
   PubMed 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;35:2249–2259.
   PubMed Web of Science ®Google Scholar
• 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;24:1454–1459.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hovingh GK, Davidson MH, Kastelein JJ, et al. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J. 2013;34:962–971.
   PubMed Web of Science ®Google Scholar
• Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, et al., editors. The metabolic and molecular bases of inherited disease. 8th ed. New York, NY: McGraw-Hill Inc.; 2001. p. 2863–2913.
   Google Scholar
• Marais AD, Raal FJ, Stein EA, et al. A dose-titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemia. Atherosclerosis. 2008;197:400–406.
   PubMed Web of Science ®Google Scholar
• Raal FJ, Pilcher GJ, Illingworth DR, et al. Expanded-dose simvastatin is effective in homozygous familial hypercholesterolaemia. Atherosclerosis. 1997;135:249–256.
   PubMed Web of Science ®Google Scholar
• 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. 2015;385:331–340.
   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;385:341–350.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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;63:2541–2548.
   PubMed Web of Science ®Google Scholar
• Nissen SE, Stroes E, Dent-Acosta RE, et al. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA. 2016;315:1580–1590.
   PubMed Web of Science ®Google Scholar
• Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370:1809–1819.
   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;372:1500–1509.
   PubMed Web of Science ®Google Scholar
• Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316:2373–2384.
   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 Mar 17. 376: 1713–1722. Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Cholesterol Treatment Trialists’ (CTT) Collaboration. 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.
   PubMed Web of Science ®Google Scholar
• Giugliano RP, Mach F, Zavitz K, et al. EBBINGHAUS Investigators. Design and rationale of the EBBINGHAUS trial: a phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy – a cognitive study of patients enrolled in the FOURIER trial. Clin Cardiol. 2017;40:59–65.
   PubMed Web of Science ®Google Scholar
• Toth PP, Descamps O2, Genest J, et al. Pooled safety analysis of evolocumab in over 6000 patients from double-blind and open-label extension studies. Circulation. 2017 Mar 1;135:1819–1831. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36:2996–3003.
   PubMed Web of Science ®Google Scholar
• Moriarty PM, Parhofer KG, Babirak SP, et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016;37:3588–3595.
   PubMed Web of Science ®Google Scholar
• Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;385:341–350.
   Google Scholar
• 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;16:906–915.
   Web of Science ®Google Scholar
• Cannon CP, Cariou B, Blom D, et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015;36:1186–1194.
   PubMed Web of Science ®Google Scholar
• Bays H, Gaudet D, Weiss R, et al. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab. 2015;100:3140–3148.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Rey J, Poitiers F, Paehler T, et al. Relationship between LDL-C, free PCSK9, and alirocumab levels after different lipid-lowering strategies. J Am Heart Assoc. 2016;5:e003323.
   PubMed Web of Science ®Google Scholar
• 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;380:29–36.
   PubMed Web of Science ®Google Scholar
• Seidah NG, Awan Z, Chretien M, et al. PCSK9: a key modulator of cardiovascular health. Circ Res. 2014;114:1022–1036.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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:pii: e003421.
   Web of Science ®Google Scholar
• Jones PH, Bays HE, Chaudhari U, et al. Safety of alirocumab (a PCSK9 monoclonal antibody) from 14 randomized trials. Am J Cardiol. 2016;118:1805–1811.
   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;134:1931–1943.
   PubMed Web of Science ®Google Scholar
• Ballantyne CM, Neutel J, Cropp A, et al. Results of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia. Am J Cardiol. 2015;115:1212–1221.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Amarenco P, Brunell R, et al. Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Investigators. Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: rationale and design of the studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) lipid lowering and SPIRE cardiovascular outcomes trials. Am Heart J. 2016;178:135–144.
   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. 2017Mar17. [Epub ahead of print].
   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 Mar 17. 376: 1517–1526. [Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Roth EM, Goldberg AC, Catapano AL, et al. Antidrug antibodies in patients treated with alirocumab. N Engl J Med. 2017 Mar 17;376:1589–1590. Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (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.
   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;376:41–51.
   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 Mar 17. 376: 1430–1440. Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Mora S, Rose L. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents. Eur Heart J. 2016;37:1373–1379.
   PubMed Web of Science ®Google Scholar
• Gouni-Berthold I, Descamps OS, Fraass U, et al. Systematic review of published phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia. Br J Clin Pharmacol. 2016;82:1412–1443.
   PubMed Web of Science ®Google Scholar