The PCSK9 revolution: Current status, controversies, and future directions

Rosenson, 2018, The evolving future of PCSK9 inhibitors, J Am Coll Cardiol, 72, 314, 10.1016/j.jacc.2018.04.054

Abifadel, 2003, Mutations in PCSK9 cause autosomal dominant hypercholesterolemia, Nat Genet, 34, 154, 10.1038/ng1161

Cohen, 2005, Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9, Nat Genet, 37, 161, 10.1038/ng1509

Cohen, 2006, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease, N Engl J Med, 354, 1264, 10.1056/NEJMoa054013

Zhao, 2006, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote, Am J Hum Genet, 79, 514, 10.1086/507488

Hooper, 2007, The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population, Atherosclerosis, 193, 445, 10.1016/j.atherosclerosis.2006.08.039

Shapiro, 2018, PCSK9: from basic science discoveries to clinical trials, Circ Res, 122, 1420, 10.1161/CIRCRESAHA.118.311227

Langslet, 2015, Evolocumab (AMG 145) for primary hypercholesterolemia, Expert Rev Cardiovasc Ther, 13, 477, 10.1586/14779072.2015.1030395

Farnier, 2015, An evaluation of alirocumab for the treatment of hypercholesterolemia, Expert Rev Cardiovasc Ther, 13, 1307, 10.1586/14779072.2015.1111759

Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med, 376, 1713, 10.1056/NEJMoa1615664

Ridker, 2017, Cardiovascular efficacy and safety of bococizumab in high-risk patients, N Engl J Med, 376, 1527, 10.1056/NEJMoa1701488

Schwartz, 2018, Alirocumab and cardiovascular outcomes after acute coronary syndrome, N Engl J Med, 379, 2097, 10.1056/NEJMoa1801174

2019

2019

Ridker, 2017, Lipid-reduction variability and antidrug-antibody formation with bococizumab, N Engl J Med, 376, 1517, 10.1056/NEJMoa1614062

Giugliano, 2017, Cognitive function in a randomized trial of evolocumab, N Engl J Med, 377, 633, 10.1056/NEJMoa1701131

Giugliano, 2017, Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial, Lancet (London, England), 390, 1962, 10.1016/S0140-6736(17)32290-0

Bonaca, 2018, Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the fourier trial (further cardiovascular outcomes research with pcsk9 inhibition in subjects with elevated risk), Circulation, 137, 338, 10.1161/CIRCULATIONAHA.117.032235

Sabatine, 2017, Clinical benefit of evolocumab in patients with a history of MI: an analysis from FOURIER

Grundy, 2018, 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, J Am Coll Cardiol

Kaufman, 2017, Application of PCSK9 inhibitors in practice: challenges and opportunities, Circ Res, 121, 499, 10.1161/CIRCRESAHA.117.311532

Kaufman, 2019, Application of PCSK9 inhibitors in practice, Circ Res, 124, 32, 10.1161/CIRCRESAHA.118.314191

Orringer, 2017, Update on the use of PCSK9 inhibitors in adults: recommendations from an expert panel of the National Lipid Association, J Clin Lipidol, 11, 880, 10.1016/j.jacl.2017.05.001

Lloyd-Jones, 2017, J Am Coll Cardiol, 70, 1785, 10.1016/j.jacc.2017.07.745

Catapano, 2016, 2016 ESC/EAS guidelines for the management of dyslipidaemias, Eur Heart J, 37, 2999, 10.1093/eurheartj/ehw272

Shapiro, 2018, Diagnosing resistance to a proprotein convertase subtilisin/Kexin type 9 inhibitor, Ann Intern Med, 168, 376, 10.7326/M17-2485

Tsimikas, 2017, A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies, J Am Coll Cardiol, 69, 692, 10.1016/j.jacc.2016.11.042

Erqou, 2009, Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality, JAMA, 302, 412, 10.1001/jama.2009.1063

Kamstrup, 2013, Extreme lipoprotein(a) levels and improved cardiovascular risk prediction, J Am Coll Cardiol, 61, 1146, 10.1016/j.jacc.2012.12.023

Clarke, 2009, Genetic variants associated with Lp(a) lipoprotein level and coronary disease, N Engl J Med, 361, 2518, 10.1056/NEJMoa0902604

Deloukas, 2013, Large-scale association analysis identifies new risk loci for coronary artery disease, Nat Genet, 45, 25, 10.1038/ng.2480

Kamstrup, 2009, Genetically elevated lipoprotein(a) and increased risk of myocardial infarction, JAMA, 301, 2331, 10.1001/jama.2009.801

O'Donoghue, 2014, Lipoprotein(a) for risk assessment in patients with established coronary artery disease, J Am Coll Cardiol, 63, 520, 10.1016/j.jacc.2013.09.042

Willeit, 2018, Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials, Lancet (London, England), 392, 1311, 10.1016/S0140-6736(18)31652-0

Warden, 2019, Impact of PCSK9 inhibitors on plasma lipoprotein(a) concentrations with or without a background of niacin therapy, J Clin Lipidol, 10.1016/j.jacl.2019.04.008

O'Donoghue, 2019, Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk, Circulation, 139, 1483, 10.1161/CIRCULATIONAHA.118.037184

Bittner, 2018, Lp(a) and cardiovascular outcomes: an analysis from the ODYSSEY OUTCOMES trial, Atheroscler Suppl, 32, 24, 10.1016/j.atherosclerosissup.2018.04.072

Raal, 2016, PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor's role, J Lipid Res, 57, 1086, 10.1194/jlr.P065334

Hoover-Plow, 2013, Lipoprotein(a) metabolism: potential sites for therapeutic targets, Metabolism, 62, 479, 10.1016/j.metabol.2012.07.024

Watts, 2018, Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics, Eur Heart J, 39, 2577, 10.1093/eurheartj/ehy122

Kostner, 2017, Lipoprotein (a): a historical appraisal, J Lipid Res, 58, 1, 10.1194/jlr.R071571

Villard, 2016, PCSK9 modulates the secretion but not the cellular uptake of lipoprotein(a) ex vivo: an effect blunted by alirocumab, JACC Basic Transl Sci, 1, 419, 10.1016/j.jacbts.2016.06.006

Rader, 1995, The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans, J Clin Invest, 95, 1403, 10.1172/JCI117794

Boffa, 2013, Update on lipoprotein(a) as a cardiovascular risk factor and mediator, Curr Atheroscler Rep, 15, 360, 10.1007/s11883-013-0360-6

Stein, 2013, Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia, Circulation, 128, 2113, 10.1161/CIRCULATIONAHA.113.004678

Saavedra, 2014, PCSK9 R46L, lower LDL, and cardiovascular disease risk in familial hypercholesterolemia: a cross-sectional cohort study, Arterioscler Thromb Vasc Biol, 34, 2700, 10.1161/ATVBAHA.114.304406

Saavedra, 2015, Familial hypercholesterolemia: PCSK9 InsLEU genetic variant and prediabetes/diabetes risk, J Clin Lipidol, 9, 786, 10.1016/j.jacl.2015.08.005

Edmiston, 2017, Discordant response of low-density lipoprotein cholesterol and lipoprotein(a) levels to monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9, J Clin Lipidol, 11, 667, 10.1016/j.jacl.2017.03.001

Shapiro, 2019, Relationship between low-density lipoprotein cholesterol and lipoprotein(a) lowering in response to pcsk9 inhibition with evolocumab, J Am Heart Assoc, 8, 10.1161/JAHA.118.010932

Sarwar, 2007, Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies, Circulation, 115, 450, 10.1161/CIRCULATIONAHA.106.637793

Dijk, 2018, Beyond LDL: what role for PCSK9 in triglyceride-rich lipoprotein metabolism?, Trends Endocrinol Metab, 29, 420, 10.1016/j.tem.2018.03.013

Filippatos, 2018, Effects of PCSK9 inhibitors on other than low-density lipoprotein cholesterol lipid variables, J Cardiovasc Pharmacol Ther, 23, 3, 10.1177/1074248417724868

Baragetti, 2018, Proprotein convertase subtilisin-Kexin type-9 (PCSK9) and triglyceride-rich lipoprotein metabolism: facts and gaps, Pharmacol Res, 130, 1, 10.1016/j.phrs.2018.01.025

Jacobson, 2015, National lipid association recommendations for patient-centered management of dyslipidemia: part 1–full report, J Clin Lipidol, 9, 129, 10.1016/j.jacl.2015.02.003

Watts, 2017, Factorial effects of evolocumab and atorvastatin on lipoprotein metabolism, Circulation, 135, 338, 10.1161/CIRCULATIONAHA.116.025080

Reyes-Soffer, 2017, Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans, Circulation, 135, 352, 10.1161/CIRCULATIONAHA.116.025253

Toth, 2016, Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo, Lipids Health Dis, 15, 28, 10.1186/s12944-016-0197-4

2018

Qamar, 2019, Interindividual variation in low-density lipoprotein cholesterol level reduction with evolocumab: an analysis of FOURIER trial data, JAMA Cardiol, 4, 59, 10.1001/jamacardio.2018.4178

Bays, 2018, Assessment of the 1% of patients with consistent < 15% reduction in low-density lipoprotein cholesterol: pooled analysis of 10 phase 3 ODYSSEY alirocumab trials, Cardiovasc Drugs Ther, 32, 175, 10.1007/s10557-018-6784-z