Are antibodies against PCSK9 the statins of the 21st century?

References

• Koren MJ, Giugliano RP, Raal FJ et al.; OSLER Investigators. 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 29(2), 234–243 (2013).
   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
• Desai NR, Giugliano RP, Zhou J et al. AMG 145, a monoclonal antibody against PCSK9, facilitates achievement of NCEP-ATP III LDL-C goals among high risk patients: an analysis from the LAPLACE-TIMI 57 trial. J. Am. Coll. Cardiol. 63(5), 430–433 (2013). • First large study with evolocumab.
   Google Scholar
• Abifadel M, Varret M, Rabes JP et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34(2), 154–156 (2003). •• First large epidemiological study to highlight the importance of PCSK9.
   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
• 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), 2497–2506 (2012). • First study with evolocumab monotherapy for statin-intolerant patients.
   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
• Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK. The PCSK9 decade. J. Lipid Res. 53(12), 2515–2524 (2012). •• The review that elucidated the role of PCSK9.
   Google Scholar
• Shan L, Pang L, Zhang R, Murgolo NJ, Lan H, Hedrick JA. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem. Biophys. Res. Commun. 375(1), 69–73 (2008).
   Google Scholar
• 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. 48(4), 763–767 (2007).
   Google Scholar
• Lindholm MW, Elmén J, Fisker N et al. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates. Mol. Ther. 20(2), 376–381 (2012).
   Google Scholar
• Mikhailidis DP, Athyros VG. Year in review 2013: dyslipidaemia in 2013: new statin guidelines and promising novel therapeutics. Nat. Rev. Cardiol. 11(2), 72–74 (2013).
   Google Scholar
• Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER). http://clinicaltrials.gov/ct2/show/NCT01764633?term=FOURIER&rank=1
   Google Scholar
• US FDA. How Drugs are Developed and Approved. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/default.htm
   Google Scholar
• Stone NJ, Robinson J, 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. J. Am. Coll. Cardiol. doi.org/10.1016/j.jacc.2013.11.002 (2013) (Epub ahead of print). •• The recent american college of cardiology (ACC)/ american heart association (AHA) lipid guidelines.
   Google Scholar
• Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Hypolipidaemic drug treatment: yesterday is not gone yet, today is challenging and tomorrow is coming soon, let us combine them all. Curr. Pharm. Des. (2014) (In press).
   Google Scholar
• Navarese EP, Buffon A, Andreotti F et al. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am. J. Cardiol. 111(8), 1123–1130 (2013). •• The meta-analysis that linked statins with new-onset diabetes.
   Google Scholar
• Leuschen J, Mortensen EM, Frei CR, Mansi EA, Panday V, Mansi I. Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol. 131(11), 1427–1434 (2013).
   Google Scholar
• Rojas-Fernandez CH, Cameron JC. Is statin-associated cognitive impairment clinically relevant? A narrative review and clinical recommendations. Ann. Pharmacother. 46(4), 549–557 (2012).
   Google Scholar
• Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP. Pleiotropic effects of statins-clinical evidence. Curr. Pharm. Des. 15(5), 479–489 (2009).
   Google Scholar
• Athyros VG, Mikhailidis DP, Papageorgiou AA et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J. Clin. Pathol. 57(7), 728–734 (2004).
   Google Scholar
• Athyros VG, Elisaf M, Papageorgiou AA et al. GREACE Study Collaborative Group: effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Am. J. Kidney Dis. 43(4), 589–599 (2004).
   Google Scholar
• Athyros VG, Tziomalos K, Gossios TD et al. GREACE Study Collaborative Group: safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study: a post-hoc analysis. Lancet 376, 1916–1922 (2010).
   Google Scholar