Doença Cardiovascular Aterosclerótica, Necessidades não Satisfeitas, e Inclisiran
DOI:
https://doi.org/10.24950/rspmi.1603Palavras-chave:
Anticolesterolémicos/uso terapêutico, Aterosclerose/ tratamento farmacológico, Doenças Cardiovasculares/tratamento farmacológico, Doenças cardiovasculares/ prevenção e controlo, Hipercolesterolemia/ tratamento farmacológico, RNA Interferente Pequeno/uso terapêuticoResumo
A doença cardiovascular aterosclerótica (DCVA) lidera as
principais causas de morte e incapacidade a nível mundial,
acarretando um pesado impacto económico, correspondente a 1% do produto interno bruto em Portugal. O desenvolvimento e progressão da DCVA encontra-se em estreita relação com a hipercolesterolemia, sendo que níveis elevados de C-LDL são o seu fator de risco mais importante e facilmente modificável. A redução do C-LDL provou diminuir a incidência de eventos cardiovasculares e as recomendações europeias advogam valores alvo de C-LDL de acordo com o risco cardiovascular do doente.
O risco da hipercolesterolemia é cumulativo, tornando-se
relevante a redução do C-LDL o mais precocemente possível.
Apesar da eficácia e segurança demonstrada pelas diversas
terapêuticas hipolipemiantes existentes, no mundo real a
maioria dos doentes não atinge os valores lipídicos recomendados. Várias limitações ao adequado controlo lipídico foram apontadas, nomeadamente a baixa adesão dos doentes ao tratamento. Inclisiran é o primeiro fármaco que permite inibir a síntese de PCSK9 através do mecanismo de RNA de interferência.
Com uma administração subcutânea semestral, após administração nos dias 1 e 90, possibilita uma redução do C-LDL superior a 50%, com bom perfil de segurança. A vantagem da sua longa duração de ação permitirá potencialmente contornar a baixa adesão dos doentes ao tratamento e aumentar a efetividade na redução do C-LDL, que se poderá traduzir na redução da morbi-mortalidade por DCVA e do seu elevado impacto económico.
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Referências
Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, 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;38:2459-72. doi: 10.1093/eurheartj/ehx144.
Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42:3227-337. doi: 10.1093/eurheartj/ehab484. Erratum in: Eur Heart J. 2022;43:4468.
GBD 2016 Mortality Collaborators. Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1084-150. doi: 10.1016/S0140-6736(17)31833-0.
Costa J, Alarcão J, Amaral-Silva A, Araújo F, Ascenção R, Caldeira D, et al. Atherosclerosis: The cost of illness in Portugal. Rev Port Cardiol. 2021;40:409-19. doi: 10.1016/j.repce.2020.08.003.
Emerging Risk Factors Collaboration; Di Angelantonio E, Gao P, Pennells L, Kaptoge S, Caslake M, et al. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307:2499-506. doi: 10.1001/jama.2012.6571.
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111-88. doi: 10.1093/eurheartj/ehz455.
Khan SA, Naz A, Qamar Masood M, Shah R. Meta-analysis of inclisiran for the treatment of hypercholesterolemia. Am J Cardiol. 2020134:69-73. doi: 10.1016/j.amjcard.2020.08.018.
Global health estimates: Leading causes of death. [accessed Jan 2022] Available at: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death.
Instituto Nacional de Estatística. Portal do INE. [accessed Jan 2022] Available at: https://www.ine.pt/xportal/xmain xpid=INE&xpgid=ine_destaques&DESTAQUESdest_boui=5944178 80&DESTAQUEStema=55538&DESTAQUESmodo=2.
INSA. Conheça o retrato da saúde em Portugal 2018 - INSA. [accessed Jan 2022] Available at: https://www.insa.min-saude.pt/conheca-o-retrato-da-saude-em-portugal-2018/.
Observatório Nacional da Diabetes. Relatório do Observatório Nacional da Diabetes – APDP. [accessed Jan 2022] Available at: https://apdp.pt/3d-flip-book/relatorio-do-observatorio-nacional-da-diabetes/.
Timmis A, Townsend N, Gale C, Grobbee R, Maniadakis N, Flather M, et al. European Society of Cardiology: Cardiovascular Disease Statistics 2017. Eur Heart J. 2018;39:508-79. doi: 10.1093/eurheartj/ehx628.
World Health Organization. Global health estimates: Leading causes of DALYs. [accessed Jan 2022] Available at: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/global-health-estimates-leading-causes-of-dalys.
Fernández-Friera L, Peñalvo JL, Fernández-Ortiz A, Ibañez B, López-Melgar B, Laclaustra M, et al. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study. Circulation. 2015;131:2104-13. doi: 10.1161/CIRCULATIONAHA.114.014310.
Wadström BN, Wulff AB, Pedersen KM, Jensen GB, Nordestgaard BG. Elevated remnant cholesterol increases the risk of peripheral artery disease, myocardial infarction, and ischaemic stroke: a cohort-based study. Eur Heart J. 2022;43:3258-69. doi: 10.1093/eurheartj/ehab705.
Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. Circ Res. 2016;118:535-46. doi: 10.1161/CIRCRESAHA.115.307611.
Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007;116:1832-44. doi: 10.1161/CIRCULATIONAHA. 106.676890.
Ference BA, Kastelein JJP, Catapano AL. Lipids and Lipoproteins in 2020. JAMA. 2020;324:595-6. doi: 10.1001/jama.2020.5685.
Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, 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;41:2313-30. doi: 10.1093/eurheartj/ehz962.
Sociedade Portuguesa de Aterosclerose. Manual de lípidos. Lisboa: Cultura Editora; 2021.
Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407-77. doi: 10.1093/eurheartj/ehz425.
Mundi S, Massaro M, Scoditti E, Carluccio MA, van Hinsbergh VWM, Iruela-Arispe ML, et al. Endothelial permeability, LDL deposition, and cardiovascular risk factors-a review. Cardiovasc Res. 2018;114:35-52. doi: 10.1093/cvr/cvx226.
Tokgözoglu L, Libby P. The dawn of a new era of targeted lipid-lowering therapies. Eur Heart J. 2022;43:3198-208. doi: 10.1093/eurheartj/ehab841.
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-78. doi: 10.1016/S0140-6736(05)67394-1.
Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A,el al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60:2631-9. doi: 10.1016/j.jacc.2012.09.017.
Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016;316:1289-97. doi: 10.1001/jama.2016.13985.
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;354:1264-72. doi: 10.1056/NEJMoa054013.
Giugliano RP, Sabatine MS, Ott BR. Cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377:1997. doi: 10.1056/NEJMc1712102.
Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, et al CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016;134:1931-43. doi: 10.1161/CIRCULATIONAHA. 116.024604.
Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532-61. doi: 10.1016/S0140-6736(16)31357-5.
Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365:2078-87. doi: 10.1056/NEJMoa1110874.
Shapiro MD, Bhatt DL. "Cholesterol-Years" for ASCVD Risk Prediction and Treatment. J Am Coll Cardiol. 2020;76:1517-20. doi: 10.1016/j. jacc.2020.08.004.
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111-88. doi: 10.1093/eurheartj/ehz455.
Cholesterol Treatment Trialists’ (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670-81. doi: 10.1016/S0140-6736(10)61350-5.
Bytyçi I, Penson PE, Mikhailidis DP, Wong ND, Hernandez AV, Sahebkar A, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022;43:3213-23. doi: 10.1093/eurheartj/ehac015.
Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009;265:568-80. doi: 10.1111/j.1365-2796.2008.02062.x.
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372:2387-97. doi: 10.1056/NEJMoa1410489.
Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P. Safety and efficacy of ezetimibe: A meta-analysis. Int J Cardiol. 2015;201:247-52. doi: 10.1016/j.ijcard.2015.08.103.
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376:1713-22. doi: 10.1056/NEJMoa1615664.
Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379:2097-107. doi: 10.1056/NEJMoa1801174.
Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489-99. doi: 10.1056/NEJMoa1501031.
Casula M, Olmastroni E, Boccalari MT, Tragni E, Pirillo A, Catapano AL. Cardiovascular events with PCSK9 inhibitors: an updated meta-analysis of randomised controlled trials. Pharmacol Res. 2019;143:143-50. doi: 10.1016/j.phrs.2019.03.021.
O'Donoghue ML, Giugliano RP, Wiviott SD, Atar D, Keech A, Kuder JF, et al. Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease. Circulation. 2022;146:1109-19. doi: 10.1161/CIRCULATIONAHA. 122.061620.
Ray KK, Ference BA, Séverin T, Blom D, Nicholls SJ, Shiba MH, et al. World Heart Federation Cholesterol Roadmap 2022. Glob Heart. 2022;17:75. doi: 10.5334/gh.1154.
De Backer G, Jankowski P, Kotseva K, Mirrakhimov E, Reiner Ž, Rydén L, et al. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis. 2019;285:135-46. doi: 10.1016/j.atherosclerosis.2019.03.014.
Ray KK, Molemans B, Schoonen WM, Giovas P, Bray S, Kiru G, et al.EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study. Eur J Prev Cardiol. 2021;28:1279-89. doi: 10.1093/eurjpc/zwaa047.
Béliard S, Boccara F, Cariou B, Carrié A, Collet X, Farnier M, et al. High burden of recurrent cardiovascular events in heterozygous familial hypercholesterolemia: The French Familial Hypercholesterolemia Registry. Atherosclerosis. 2018;277:334-40. doi: 10.1016/j.atherosclerosis.2018.08.010.
da Silva PM, Cardoso SM; Investigadores do Estudo DYSIS Portugal. Persistent lipid abnormalities in patients treated with statins: Portuguese results of the Dyslipidemia International Study (DYSIS). Rev Port Cardiol. 2011;30:47-63.
Bourbon M, Alves AC, Rato Q. Prevalência de fatores de risco cardiovascular na população portuguesa: Relatório estudo e_COR. (2019).
da Silva PM, Aguiar C, Morais J; DISGEN-LIPID study Investigators. Suboptimal lipid levels in clinical practice among Portuguese adults with dyslipidemia under lipid-lowering therapy: Data from the DISGEN-LIPID study. Rev Port Cardiol. 2019;38:559-69. doi: 10.1016/j.repc.2019.02.009.
Gavina C. Cardiovascular risk profile in Portugal: evidence from a large population-based cohort. Eur Heart J. 2012;42:ehab724–2480.
Gavina C, Carvalho DS, Pardal M, Afonso-Silva M, Grangeia D, Dinis-Oliveira RJ, et al. Cardiovascular Risk Profile and Lipid Management in the Population-Based Cohort Study LATINO: 20 Years of Real-World Data. J Clin Med. 2022;11:6825. doi: 10.3390/jcm11226825.
Santos RD, Bourbon M, Alonso R, Cuevas A, Vasques-Cardenas NA, Pereira AC, et al. Clinical and molecular aspects of familial hypercholesterolemia in Ibero-American countries. J Clin Lipidol. 2017;11:160-6. doi: 10.1016/j.jacl.2016.11.004.
Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascular outcomes. Circulation. 2009;119:3028-35. doi: 10.1161/CIRCULATIONAHA.108.768986.
Kini V, Ho PM. Interventions to Improve Medication Adherence: A Review. JAMA. 2018 Dec 18;320(23):2461-73. doi: 10.1001/jama.2018.19271.
Kotseva K, De Backer G, De Bacquer D, Rydén L, Hoes A, Grobbee D, et al. Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry. Eur J Prev Cardiol. 2019;26:824-35. doi: 10.1177/2047487318825350.
Mello e Silva A. Heaven can wait… for lipid control in very high cardiovascular risk patients. Rev Port Cardiol. 2021;40:649-51. doi: 10.1016/j. repce.2021.08.005. 58. Pedro AR, Amaral O, Escoval A. Literacia em saúde, dos dados à ação: tradução, validação e aplicação do European Health Literacy Survey em Portugal. Rev Port Saúde Pública. 2016; 34:259–75.
Galve E, Cordero A, Cequier A, Ruiz E, González-Juanatey JR. Degree of Lipid Control in Patients With Coronary Heart Disease and Measures Adopted by Physicians. REPAR Study. Rev Esp Cardiol. 2016;69:931-8. doi: 10.1016/j.rec.2016.02.012.
Scicchitano P, Milo M, Mallamaci R, De Palo M, Caldarola P, Massari F, et al. Inclisiran in lipid management: A Literature overview and future perspectives. Biomed Pharmacother. 2021;143:112227. doi: 10.1016/j.biopha. 2021.112227.
Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382:1507-19. doi: 10.1056/NEJMoa1912387.
Sinning D, Landmesser U. Low-density Lipoprotein-Cholesterol Lowering Strategies for Prevention of Atherosclerotic Cardiovascular Disease: Focus on siRNA Treatment Targeting PCSK9 (Inclisiran). Curr Cardiol Rep. 2020;22:176. doi: 10.1007/s11886-020-01427-6.
Ray KK, Raal FJ, Kallend DG, Jaros MJ, Koenig W, Leiter LA, et al. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J. 2023;44:129-38. doi: 10.1093/eurheartj/ehac594.
Team R. Reimbursement Team. Inclisiran (Leqvio). Can J Health Technol. 2022 (in press). doi: 10.51731/cjht.2022.272 (2022).
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