PURPOSE OF REVIEW: PCSK9 inhibitors have been shown to be the most effective class of drugs modifying the levels of LDL-cholesterol as the main risk factor for atherosclerotic cardiovascular disease. The aim of this paper is to assess the effect of monoclonal antibodies on lipid and lipoprotein metabolism in real-world practice. RECENT FINDINGS: The outcome trials showed effective reduction of LDL-C by 56-62%. Landmark studies enrolling over a total of 46,000 patients with CHD in their medical history demonstrated the beneficial effect of both agents on cardiovascular morbidity and mortality. The data from real everyday clinical practice are very limited or missing. Even in real-world practice, PCSK9 inhibitors have been shown to be an effective, safe, and well-tolerated class of drugs with effects comparable with those reported from large randomized controlled trials.

Center of Preventive Cardiology 3rd Department of Internal Medicine General University Hospital 1st Faculty of Medicine Charles University Prague Prague Czech Republic

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Townsend N, Wilson L, Bhatnagar P, et al. Cardiovascular disease in Europe: Epidemiological update 2016. Eur Heart J. 2016;37(42):3232–3245. doi: 10.1093/eurheartj/ehw334. PubMed DOI

Mach F, Baigent C, Catapano AL, et al. [ESC Scientific Document Group]. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. doi: 10.1093/eurheartj/ehz455. PubMed DOI

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. 2006;354(12):1264–1272. doi: 10.1056/NEJMoa054013. PubMed DOI

Cohen J, Pertsemlidis A, Kotowski IK, et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37(2):161–165. doi: 10.1038/ng1509. PubMed DOI

Češka R, Táborský M, Vrablík M. Společné stanovisko odborných společností k předepisování PCSK9-inhibitorů. AtheroRev. 2018;3(3):201–207.

Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: A systematic review and meta-analysis. Ann Intern Med. 2015;163(1):40–51. doi: 10.7326/M14-2957. PubMed DOI

Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722. doi: 10.1056/NEJMoa1615664. PubMed DOI

Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–2107. doi: 10.1056/NEJMoa1801174. PubMed DOI

Poirier S, Mayer G, Poupon V, et al. Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: Evidence for an intracellular route. J Biol Chem. 2009;284(42):28856–28864. doi: 10.1074/jbc.M109.037085. PubMed DOI PMC

Reiner Z, De Backer G, Fras Z, et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries--Findings from the EUROASPIRE IV survey. Atherosclerosis. 2016;246:243–250. doi: 10.1016/j.atherosclerosis.2016.01.018. PubMed DOI

Bruthans J, Mayer O, Galovcova M, et al. State of secondary prevention in Czech coronary patients in the EUROASPIRE IV study. Cor Vasa. 2014;56(2):e105–e112. doi: 10.1016/j.crvasa.2014.02.012. DOI

Zlatohlavek L, Snejdrlova M, Bridges I, et al. Observational study of dyslipidemia management in the Czech Republic. Athero Rev. 2019;4(3):162–169.

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. 2012;126(20):2408–2417. doi: 10.1161/CIRCULATIONAHA.112.144055. PubMed DOI

Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37(39):2999–3058. doi: 10.1093/eurheartj/ehw272. PubMed DOI

Lipinski MJ, Benedetto U, Escarcega RO, et al. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J. 2016;37(6):536–545. doi: 10.1093/eurheartj/ehv563. PubMed DOI

Regional differences in physicians' behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study

Familial Hypercholesterolemia: Real-World Data of 1236 Patients Attending a Czech Lipid Clinic. A Retrospective Analysis of Experience in More than 50 years. Part II. Clinical Characteristics