Inklisiran and its role in lipid-lowering therapy

Czech version

Authors: Olga Bobelová
Authors‘ workplace: DIOLI s. r. o., Košice
Published in: Diab Obez 2024; 24(1): 25-32
Category: Reviews

Overview

Cardiovascular disease continues to top morbidity and mortality rankings worldwide. Most of these diseases are atherosclerotic in origin, such as myocardial infarction or stroke. Elevated LDL-cholesterol (LDL-C) concentration is a major risk factor directly involved in the development of atherosclerosis. The high concentration and the length of exposure to elevated LDL-C are crucial for the degree of cardiovascular risk of a patient.

Keywords:

stroke – myocardial infarction – Atherosclerosis – cardiovascular disease – cardiovascular risk – LDL-cholesterol (LDL-C)

Sources

Ference BA, Ray KK, Catapano AL et al. Mendelian Randomization study of ACLY and cardiovascular disease. N Engl J Med 2019; 380(11): 1033–1042. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1806747>.

Ference BA, Ginsberg HN, Graham I et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel. Eur Heart J 2017; 38(12): 2459–2472. Dostupné z DOI: <https://doi.org/10.1093/eurheartj/ehx144>.

Ference BA, Robinson JG, Brook RD et al. Variation in PCSK9 and HMGCR and risk of cardiovascular disease and diabetes. N Engl J Med 2016; 375(22): 2144–2153. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1604304>.

Najam O, Lambert G, Ray KK. The past, present and future of lipid lowering therapy. Clin Lipidol 2015; 10(6): 481–498. Dostupné z DOI: <http://dx.doi.org/10.2217/clp.15.40>.

Macchi C, Sirtori CR, Corsini A et al. A new Dawn for managing dyslipidemias: the era of RNA-based therapies. Pharmacol Res 2019; 150: 104413. Dostupné z DOI: <https://doi.org/10.1016/j.phrs.2019.104413>.

European Medicines Agency. Leqvio (inclisiran). Dostupné z WWW: <https://www.ema.europa.eu/en/documents/overview/leqvio-epar-medicine-overview_en.pdf(accessed>.

US Food and Drug Administration. Leqvio® (inclisiran) injection, for subcutaneous use Initial U.S. Approval: 2021. Dostupné z WWW: <https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=214012>.

Raal FJ, Kallend D, Ray KK et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. N Engl J Med 2020; 382(16): 1520–1530. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1913805>.

Ray KK, Wright RS, Kallend D et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med 2020; 382(16): 1507–1519. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1912387>.

Wright RS, Ray KK, Raal FJ et al. Pooled patient-level analysis of inclisiran trials in patients with familial hypercholesterolemia or atherosclerosis. J Am Coll Cardiol 2021; 77(9): 1182–1193. Dostupné z DOI: <https://doi.org/10.1016/j.jacc.2020.12.058>.

Yusuf S, Peto R, Lewis J et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985; 27(5): 335–371. Dostupné z DOI: <https://doi.org/10.1016/s0033–0620(85)80003–7>.

Silverman MG, Ference BA, Im K et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA 2016; 316(12): 1289–1297. Dostupné z DOI: <https://doi.org/10.1001/jama.2016.13985>

Boren J, Chapman MJ, Krauss RM et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European atherosclerosis society consensus panel. Eur Heart J 2020; 41(24): 2313–2330. Dostupné z DOI: <https://doi.org/10.1093/eurheartj/ehz962>.

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. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1615664>.

O’Donoghue ML, Giugliano RP, Wiviott SD et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation 2022; 146(15): 1109–1119. Dostupné z DOI: <https://doi.org/10.1161/ CIRCULATIONAHA.122.061620>.

Steg PG, Szarek M, Bhatt DL et al. Effect of alirocumab on mortality after acute coronary syndromes. Circulation 2019; 140(2): 103–112. Dostupné z DOI: <https://doi.org/10.1161/CIRCULATIONAHA.118.038840>.

Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372(16): 1489–1499. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1501031>.

Gaba P, Bhatt DL, Giugliano RP et al. Comparative reductions in investigator-reported and adjudicated ischemic events in REDUCE-IT. J Am Coll Cardiol 2021; 78(15): 1525–1537. Dostupné z DOI: <https://doi.org/10.1016/j.jacc.2021.08.009>.

Easton JD, Denison H, Evans SR et al. Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial. Int J Stroke 2019; 14(9): 908–914. Dostupné z DOI: <https://doi.org/10.1177/1747493019851282>.

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. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1801174>.

Sabatine MS, Giugliano RP, Wiviott SD et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372(16): 1500–1509. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1500858>.

Ray KK, Raal FJ, Kallend DG et al. [ORION Phase III investigators]. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials, Eur Heart J 2023; 44( 2): 129–138. Dostupné z DOI: <https://doi.org/10.1093/eurheartj/ehac594>.