Emerging PCSK9 inhibitors for treating dyslipidaemia: buttressing the gaps in coronary prevention

Bibliography

• Mendis S, Puska P, Norrving B. editors. Global atlas on cardiovascular disease prevention and control. Geneva, Switzerland: World Health Organisation; 2011
   Google Scholar
• Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 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:S1-45
   PubMed Web of Science ®Google Scholar
• Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818
   PubMed Web of Science ®Google Scholar
• Ference BA, Mahajan N. The role of early LDL lowering to prevent the onset of atherosclerotic disease. Curr Atheroscler Rep 2013;15:312
   PubMed Web of Science ®Google Scholar
• Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:S76-99
   PubMed Web of Science ®Google Scholar
• Assmann G, Cullen P, Schulte H. The Munster Heart Study: results of follow-up at 8 years. Eur Heart J 1998;19(Suppl A):A2-11
   PubMedGoogle Scholar
• Martin MJ, Browner WS, Hulley SB, et al. Serum cholesterol, blood pressure and mortality: implications from a cohort of 361 662 men. Lancet 1986;328:933-6
   Google Scholar
• Burnett JR, Bell DA, Hooper AJ, Hegele RA. Clinical utility gene card for: familial hypobetalipoproteinaemia (APOB). Eur J Hum Genet 2012;20. Available from: http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2014225a.html 10.1038/ejhg.2012.85
   Web of Science ®Google Scholar
• Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 2011;4:337-45
   PubMed Web of Science ®Google Scholar
• Watts GF, Gidding S, Wierzbicki AS, et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol 2014;171:309-25
   PubMed Web of Science ®Google Scholar
• Keen HI, Krishnarajah J, Bates TR, Watts GF. Statin myopathy: the fly in the ointment for the prevention of cardiovascular disease in the 21st century? Expert Opin Drug Saf 2014;13:1227-39
   PubMed Web of Science ®Google Scholar
• Leren TP. Sorting an LDL receptor with bound PCSK9 to intracellular degradation. Atherosclerosis 2014;237:76-81
   PubMed Web of Science ®Google Scholar
• Dadu RT, Ballantyne CM. Lipid lowering with PCSK9 inhibitors. Nat Rev Cardiol 2014;11:563-75
   PubMed Web of Science ®Google Scholar
• Seidah NG, Awan Z, Chretien M, Mbikay M. PCSK9: a key modulator of cardiovascular health. Circ Res 2014;114:1022-36
   PubMed Web of Science ®Google Scholar
• Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation 2004;109:III39-43
   PubMed Web of Science ®Google Scholar
• Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81
   PubMed Web of Science ®Google Scholar
• Linden F, Domschke G, Erbel C, et al. Inflammatory therapeutic targets in coronary atherosclerosis-from molecular biology to clinical application. Front Physiol 2014;5:455
   PubMed Web of Science ®Google Scholar
• Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010;375:1875-84
   PubMed Web of Science ®Google Scholar
• Lee M, Saver JL, Towfighi A, et al. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis 2011;217:492-8
   PubMed Web of Science ®Google Scholar
• Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371:203-12
   PubMed Web of Science ®Google Scholar
• Cannon CP; On behalf of the IMPROVE-IT Investigators. IMPROVE-IT Trial: A comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndromes. In: Proceedings of the American Heart Association Scientific Sessions; Chicago, USA; 2014. Available from: http://my.americanheart.org/professional/Sessions/ScientificSessions/ScienceNews/SS14-Late-Breaking-Clinical-Trials_UCM_468855_Article.jsp
   Google Scholar
• Koschinsky M, Boffa M. Lipoprotein(a) as a therapeutic target in cardiovascular disease. Expert Opin Ther Targets 2014;18:747-57
   PubMed Web of Science ®Google Scholar
• Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 2010;31:2844-53
   PubMed Web of Science ®Google Scholar
• Koschinsky ML, Boffa MB. Lipoprotein(a): An important cardiovascular risk factor and a clinical conundrum. Endocrinol Metab Clin North Am 2014;43:949-62
   PubMed Web of Science ®Google Scholar
• Nestel PJ, Barnes EH, Tonkin AM, et al. Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease. Arterioscler Thromb Vasc Biol 2013;33:2902-8
   PubMed Web of Science ®Google Scholar
• O’Donoghue ML, Morrow DA, Tsimikas S, et al. Lipoprotein(a) for risk assessment in patients with established coronary artery disease. J Am Coll Cardiol 2014;63:520-7
   PubMed Web of Science ®Google Scholar
• Bos S, Yayha R, van Lennep JE. Latest developments in the treatment of lipoprotein(a). Curr Opin Lipidol 2014;25:452-60
   PubMed Web of Science ®Google Scholar
• Leebmann J, Roeseler E, Julius U, et al. Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study. Circulation 2013;128:2567-76
   PubMed Web of Science ®Google Scholar
• Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab 2012;97:3956-64
   PubMed Web of Science ®Google Scholar
• Sjouke B, Kusters DM, Kindt I, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J 2015;36(9):560-5
   PubMed Web of Science ®Google Scholar
• Page MM, Ekinci EI, Jones RM, et al. Liver transplantation for the treatment of homozygous familial hypercholesterolaemia in an era of emerging lipid-lowering therapies. Intern Med J 2014;44:601-4
   PubMed Web of Science ®Google Scholar
• Besseling J, Kindt I, Hof M, et al. Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers. Atherosclerosis 2014;233:219-23
   PubMed Web of Science ®Google Scholar
• Joy TR, Hegele RA. Narrative review: statin-related myopathy. Ann Intern Med 2009;150:858-68
   PubMed Web of Science ®Google Scholar
• Mancini GB, Tashakkor AY, Baker S, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update. Can J Cardiol 2013;29:1553-68
   PubMed Web of Science ®Google Scholar
• Heeschen C, Hamm CW, Laufs U, et al. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002;105:1446-52
   PubMed Web of Science ®Google Scholar
• Wei L, Wang J, Thompson P, et al. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart 2002;88:229-33
   PubMed Web of Science ®Google Scholar
• Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007;297:177-86
   PubMed Web of Science ®Google Scholar
• Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J 2008;155:772-9
   PubMed Web of Science ®Google Scholar
• Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation 2006;114:2788-97
   PubMed Web of Science ®Google Scholar
• Needham M, Mastaglia FL. Statin myotoxicity: a review of genetic susceptibility factors. Neuromuscul Disord 2014;24:4-15
   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;158:526-34
   PubMed Web of Science ®Google Scholar
• Simons LA, Ortiz M, Calcino G. Long term persistence with statin therapy – experience in Australia 2006-2010. Aust Fam Physician 2011;40:319-22
   PubMed Web of Science ®Google Scholar
• McGinnis B, Olson KL, Magid D, et al. Factors related to adherence to statin therapy. Ann Pharmacother 2007;41:1805-11
   PubMed Web of Science ®Google Scholar
• Bruckert E, Hayem G, Dejager S, et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study. Cardiovasc Drugs Ther 2005;19:403-14
   PubMed Web of Science ®Google Scholar
• Backes JM, Venero CV, Gibson CA, et al. Effectiveness and tolerability of every-other-day rosuvastatin dosing in patients with prior statin intolerance. Ann Pharmacother 2008;42:341-6
   PubMed Web of Science ®Google Scholar
• Meek C, Wierzbicki AS, Jewkes C, et al. Daily and intermittent rosuvastatin 5 mg therapy in statin intolerant patients: an observational study. Curr Med Res Opin 2012;28:371-8
   PubMed Web of Science ®Google Scholar
• Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J 2013;166:597-603
   PubMed Web of Science ®Google Scholar
• Joy TR, Monjed A, Zou GY, et al. N-of-1 (single-patient) trials for statin-related myalgia. Ann Intern Med 2014;160:301-10
   PubMed Web of Science ®Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354:1264-72
   PubMed Web of Science ®Google Scholar
• Abifadel M, Varret M, Rabès J-P, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154-6
   PubMed Web of Science ®Google Scholar
• Mabuchi H, Nohara A, Noguchi T, et al. Genotypic and phenotypic features in homozygous familial hypercholesterolemia caused by proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutation. Atherosclerosis 2014;236:54-61
   PubMed Web of Science ®Google Scholar
• Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013;127:2403-13
   PubMed Web of Science ®Google Scholar
• Zhang D-W, Lagace TA, Garuti R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem 2007;282:18602-12
   PubMed Web of Science ®Google Scholar
• Urban D, Pöss J, Böhm M, Laufs U. Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 2013;62:1401-8
   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;383:60-8
   PubMed Web of Science ®Google Scholar
• Clinicaltrials.gov. A study of LY3015014 in participants with high cholesterol [Internet]. US National Institutes of Health; 2014. Available from: https://clinicaltrials.gov/ct2/show/study/NCT01890967?term=ly3015014&rank=2 [Cited 7 January 2015]
   Google Scholar
• Koren MJ, Giugliano RP, Raal FJ, et al. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation 2014;129:234-43
   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;370:1809-19
   PubMed Web of Science ®Google Scholar
• Roth EM, Taskinen MR, Ginsberg HN, et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24-week, double-blind, randomized Phase 3 trial. Int J Cardiol 2014;176:55-61
   PubMed Web of Science ®Google Scholar
• Gaudet D, Kereiakes DJ, McKenney JM, et al. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol 2014;114:711-15
   PubMed Web of Science ®Google Scholar
• Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007;370:1829-39
   PubMed Web of Science ®Google Scholar
• Amarenco P, Bogousslavsky J, Callahan A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549-59
   PubMed Web of Science ®Google Scholar
• McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke 2012;43:2149-56
   PubMed Web of Science ®Google Scholar
• McGuinness B, O’Hare J, Craig D, et al. Cochrane review on ‘Statins for the treatment of dementia’. Int J Geriatr Psychiatry 2013;28:119-26
   PubMed Web of Science ®Google Scholar
• Everett BM, Mora S, Glynn RJ, et al. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (< 30 mg/dl) with rosuvastatin 20 mg daily (from JUPITER). Am J Cardiol 2014;114:1682-9
   PubMed Web of Science ®Google Scholar
• Roth EM, McKenny JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med 2012;367:1891-900
   PubMed Web of Science ®Google Scholar
• Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia: results of a randomised, double-blind, placebo-controlled trial. Lancet 2015;385(9965):331-40
   PubMed Web of Science ®Google Scholar
• Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia: results of a randomised, double-blind, placebo-controlled trial. Lancet 2015;385(9965):341-50
   PubMed Web of Science ®Google Scholar
• Harada-Shiba M, Kishimoto I, Makino H, et al. Efficacy of evolocumab (AMG 145) in patients with PCSK9 gain-of-function mutations [abstract]. Atherosclerosis 2014;235:e11
   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;63:2541-8
   PubMed Web of Science ®Google Scholar
• Cho L, Rocco M, Colquhoun D, et al. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol 2014;37:131-9
   PubMed Web of Science ®Google Scholar
• Moriarty PM, Thompson PD, Cannon CP, et al. Odyssey Alternative: Efficacy and safety of the proproptein convertase subtilisin/kexin type 9 monoclonal antibody, alirocumab, versus ezetimibe, in patients with statin intolerance as defined by a placebo run-in and statin rechallenge arm. In: Proceedings of the 2014 American Heart Association Scientific Sessions; Chicago, USA; 2014. Available from: http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_469597.pdf
   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. [Epub ahead of print]
   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. [ Epub ahead of print]
   Web of Science ®Google Scholar
• 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;381:40-6
   PubMed Web of Science ®Google Scholar
• Hooper AJ, Burnett JR, Watts GF. Contemporary aspects of the biology and therapeutic regulation of the microsomal triglyceride transfer protein. Circ Res 2015;116:193-205
   PubMed Web of Science ®Google Scholar
• 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;33:1142-9
   PubMed Web of Science ®Google Scholar
• McGowan MP, Tardif J-C, Ceska R, et al. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS One 2012;7:e49006
   PubMed Web of Science ®Google Scholar
• 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;126:2283-92
   PubMed Web of Science ®Google Scholar
• 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;375:955-1052
   PubMed Web of Science ®Google Scholar
• Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010;363:1341-50
   PubMed Web of Science ®Google Scholar
• 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;306:2099-109
   PubMed Web of Science ®Google Scholar
• Cannon CP, Shah S, Dansky HM, et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med 2010;363:2406-15
   PubMed Web of Science ®Google Scholar
• Rader DJ, Ruotolo G, Kane JP, et al. Effects of the cholesteryl ester transfer protein inhibitor, evacetrapib, administered as monotherapy or in combination with statins on cholesterol efflux and HDL particles in patients with dyslipidemia. In: Proceedings of the American Heart Association Scientific Sessions; Chicago, USA; 2014. Available from: http://aha.scientificposters.com/epsAbstractAHA.cfm?id=14
   Google Scholar
• Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 2014;371:2383-93
   PubMed Web of Science ®Google Scholar
• Dong B, Singh AB, Fung C, et al. CETP inhibitors downregulate hepatic LDL receptor and PCSK9 expression in vitro and in vivo through a SREBP2 dependent mechanism. Atherosclerosis 2014;235:449-62
   PubMed Web of Science ®Google Scholar
• Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012;367:2089-99
   PubMed Web of Science ®Google Scholar
• Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109-22
   PubMed Web of Science ®Google Scholar
• Nikolic D, Mikhailidis DP, Davidson MH, et al. ETC-1002: a future option for lipid disorders? Atherosclerosis 2014;237:705-10
   PubMed Web of Science ®Google Scholar
• Chaparro-Riggers J, Liang H, DeVay RM, et al. Increasing serum half-life and extending cholesterol lowering in vivo by engineering an antibody with pH-sensitive binding to PCSK9. J Biol Chem 2012;287(14):11090-7
   PubMed Web of Science ®Google Scholar
• Vogt A, Parhofer KG. The potential of mipomersen, an apoB synthesis inhibitor, to reduce necessity for LDL-apheresis in patients with heterozygous familial hypercholesterolemia and coronary artery disease. Expert Opin Pharmacother 2013;14:691-7
   PubMed Web of Science ®Google Scholar
• Parhofer KG. How will new medications affect the lipoprotein apheresis situation in Germany? Atheroscler Suppl 2013;14:71-2
   PubMed Web of Science ®Google Scholar
• Ballantyne CM, Neutel J, Cropp A, et al. Efficacy and safety of bococizumab (RN316/PF-04950615), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 in statin-treated hypercholesterolemic subjects: results from a randomized, placebo-controlled, dose-ranging study (NCT: 01592240). In: Proceedings of the American College of Cardiology Scientific Sessions; Washington DC, USA; 2014. Available from: http://dx.doi.org/10.1016/S0735-1097(14)61374-7
   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
• Tingley W, Luca D, Leabman M, et al. Effects of RG7652, a fully human mAb against proprotein convertase subtilisin/kexin type 9, on LDL-C: a Phase I, randomised, double-blind, placebo-controlled, single- and multiple-dose study. Eur Heart J 2013;34:767
   PubMed Web of Science ®Google Scholar
• Stein EA, Kasichayanula S, Turner T, et al. LDL cholesterol reduction with BMS-962476, an adnectin inhibitor of PCSK9: results of a single ascending dose study [abstract]. J Am Coll Cardiol 2014;63:61372-3
   Google Scholar
• Page MM, Stefanutti C, Sniderman A, Watts GF. Recent advances in the understanding and care of familial hypercholesterolaemia: significance of the biology and therapeutic regulation of proprotein convertase subtilisin/kexin type 9. Clin Sci 2015
   PubMed Web of Science ®Google Scholar