Reduction of LDL-C levels with AMG-145, a monoclonal antibody against PCSK9, in heterozygous familial hypercholesterolemia: the RUTHERFORD study

References

• Hopkins PN, Toth PP, Ballantyne CM, Rader DJ. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J. Clin. Lipidol. 5(Suppl. 3), S9–S17 (2011).
   Google Scholar
• Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J. Lipid Res. 50(Suppl.), S172–S177 (2009).
   Google Scholar
• Abifadel M, Varret M, Rabes JP et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34(2), 154–156 (2003).
   Google Scholar
• Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354(12), 1264–1272 (2006).
   Google Scholar
• Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am. J. Epidemiol. 160(5), 407–420 (2004).
   Google Scholar
• Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am. J. Epidemiol. 160(5), 421–429 (2004).
   Google Scholar
• Ito MK, McGowan MP, Moriarty PM. Management of familial hypercholesterolemias in adult patients: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J. Clin. Lipidol. 5(Suppl. 3), S38–S45 (2011).
   Google Scholar
• Rhainds D, Arsenault BJ, Tardif JC. PCSK9 inhibition and LDL cholesterol lowering: the biology of an attractive therapeutic target and critical review of the latest clinical trials. Clin. Lipidol. 7(6), 621–640 (2012).
   Google Scholar
• Sullivan D, Olsson AG, Scott R et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the Gauss randomized trial. JAMA 308(23), 1–10 (2012).
   Google Scholar
• 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 380(9858), 1995–2006 (2012).
   Google Scholar
• 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 380(9858), 2007–2017 (2012).
   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 380(9836), 29–36 (2012).
   Google Scholar
• McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. 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. 59(25), 2344–2353 (2012).
   Google Scholar
• Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N. Engl. J. Med. 367(20), 1891–1900 (2012).
   Google Scholar
• 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 126(20), 2408–2417 (2012).
   Google Scholar
• Raal F, Panz V, Immelman A, Pilcher G. Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy. J. Am. Heart Assoc. 2(2), e000028 (2013).
   Google Scholar
• Stein EA. Other therapies for reducing low-density lipoprotein cholesterol: medications in development. Endocrinol. Metab. Clin. North Am. 38(1), 99–119 (2009).
   Google Scholar
• Stein EA, Strutt K, Southworth H, Diggle PJ, Miller E. Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia. Am. J. Cardiol. 92(11), 1287–1293 (2003).
   Google Scholar
• Stein EA, Ose L, Retterstol K et al. Further reduction of low-density lipoprotein cholesterol and C-reactive protein with the addition of ezetimibe to maximum-dose rosuvastatin in patients with severe hypercholesterolemia. J. Clin. Lipidol. 1(4), 280–286 (2007).
   Google Scholar
• Pijlman AH, Huijgen R, Verhagen SN et al. Evaluation of cholesterol lowering treatment of patients with familial hypercholesterolemia: a large cross-sectional study in The Netherlands. Atherosclerosis 209(1), 189–194 (2010).
   Google Scholar