Modern strategy of treatment hypercholesterolemia
Keywords:coronary heart disease, familial hypercholesterolemia, statins, monoclonal antibody to the proprotein convertase subtilisin/kexin type 9
Aim. The main factors of cardiovascular risk, particularly hypercholesterolemia, in patients with coronary heart disease are considered, comparative characteristic of the statins efficiency is given, and factors that determine the effectiveness of intolerance and lack of a standard hypocholesterolemia therapy are described. From the point of view of genetics is considered a promising direction of research on the development of monoclonal antibodies to the proprotein convertase subtilisin / kexin type 9, and their effect on the lipid profile in patients at high risk.
Conclusions. Statins are the main agents in the treatment and prevention of coronary heart disease. PCSK9 is an important regulator of LDL cholesterol through the effect on LDL receptors. Blocking the PCSK9 is a new mechanism in reducing LDL cholesterol
Steg, P. G., Ferrari, R., Ford, I. et al. CLARIFY Investigators (2012). Heart rate and use of beta-blockers in stable outpatients with coronary artery disease. Public Library of Science One, 7 (5), 362–384. doi: 10.1371/journal.pone.0036284
Reiner, Ž., Catapano, A. L., Backer, G., Graham, I. et al. (2011). 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). European Heart Journal, 32 (14), 1769–1818. doi: 10.1093/eurheartj/ehr158
Montalescot, G., Sechtem, U., Achenbach, S. et al. (2013). 2013 ESC guidelines on the management of stable coronary artery disease. The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. European Heart Journal, 34 (38), 2949–3003. doi: 10.1093/eurheartj/eht296
Baigent, C., Blackwell, L., Emberson, J. et. al. (2010). Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet, 376 (9753), 1670–1681. doi: 10.1016/s0140-6736(10)61350-5
Rosenson, R. S. (2004). Current overview of statin-induced myopathy. The American Journal of Medicine, 116 (6), 408–416. doi: 10.1016/j.amjmed.2003.10.033
Humphries, S. E., Whittall, R. A., Hubbart, C. S., Maplebeck, S., Cooper, J. A. (2006). Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. Journal of Medical Genetics, 43 (12), 943–949. doi: 10.1136/jmg.2006.038356
Goldstein, J. L., Brown, M. S. (2009). The LDL receptor. Arteriosclerosis Thrombosis and Vascular Biology, 29 (4), 431–438. doi: 10.1161/atvbaha.108.179564
Lambert, G., Sjouke, B., Choque, B., Kastelein, J. J. P., Hovingh, G. K. (2012). The PCSK9 decade. Journal of Lipid Research, 53 (12), 2515–2524. doi: 10.1194/jlr.r026658
Awan, Z., Seidah, N. G., MacFadyen, J. G., Benjannet, S., Chasman, D. I., Ridker, P. M., Genest, J. (2011). Rosuvastatin, Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations, and LDL Cholesterol Response: the JUPITER Trial. Clinical Chemistry, 58 (1), 183–189. doi: 10.1373/clinchem.2011.172932
Dias, C. S., Shaywitz, A. J., Wasserman, S. M. et al. (2012). Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. Journal of the American College of Cardiology, 60, 1888–1898.
Giugliano, R. P., Desai, N. R., Kohli, P., Rogers, W. J., Somaratne, R., Huang, F. et. al. (2012). 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. The Lancet, 380 (9858), 2007–2017. doi: 10.1016/s0140-6736(12)61770-x
Koren, M. J., Scott, R., Kim, J. B., Knusel, B., Liu, T., Lei, L. et. al. (2012). 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. The Lancet, 380 (9858), 1995–2006. doi: 10.1016/s0140-6736(12)61771-1
McKenney, J. M., Koren, M. J., Kereiakes, D. J., Hanotin, C., Ferrand, A.-C., Stein, E. A. (2012). 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. Journal of the American College of Cardiology, 59 (25), 2344–2353. doi: 10.1016/j.jacc.2012.03.007
Sullivan, D., Olsson, A. G., Scott, R., Kim, J. B., Xue, A., Gebski, V. et. al. (2012). Effect of a Monoclonal Antibody to PCSK9 on Low-Density Lipoprotein Cholesterol Levels in Statin-Intolerant Patients. Journal of the American Medical Association, 308 (23), 2497–2506. doi: 10.1001/jama.2012.25790
Raal, F., Scott, R., Somaratne, R., Bridges, I., Li, G., Wasserman, S. M., Stein, E. A. (2012). 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. doi: 10.1161/circulationaha.112.144055
Roth, E. M., McKenney, J. M., Hanotin, C., Asset, G., Stein, E. A. (2012). Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia. New England Journal of Medicine, 367 (20), 1891–1900. doi: 10.1056/nejmoa1201832
Stein, E. A., Mellis, S., Yancopoulos, G. D. et al. (2012). Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. New England Journal of Medicine, 366 (25), 1108–1118. doi: 10.1056/nejmc1204929
Schwartz, G. G., Bessac, L., Berdan, L. G., Bhatt, D. L., Bittner, V., Diaz, R. et. al. (2014). Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: Rationale and design of the ODYSSEY Outcomes trial. American Heart Journal, 168 (5), 682–689.e1. doi: 10.1016/j.ahj.2014.07.028
Copyright (c) 2015 Игорь Владимирович Кузнецов
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.
Authors, who are published in this journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.