Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors

Jose Seijas-Amigo, Mónica Gayoso-Rey, María José Mauriz-Montero, Pedro Suarez-Artime, Antonia Casas-Martinez, María Dominguez-Guerra, Lara Gonzalez-Freire, Ana Estany-Gestal, Alberto Codero-Fort, Moisés Rodriguez-Mañero, Jose Ramón Gonzalez-Juanatey, e investigadores MEMOGAL, Jose Seijas-Amigo, Mónica Gayoso-Rey, María José Mauriz-Montero, Pedro Suarez-Artime, Antonia Casas-Martinez, María Dominguez-Guerra, Lara Gonzalez-Freire, Ana Estany-Gestal, Alberto Codero-Fort, Moisés Rodriguez-Mañero, Jose Ramón Gonzalez-Juanatey, e investigadores MEMOGAL

Abstract

Objectives: MEMOGAL study (NCT04319081) is aimed at evaluating changes in cognitive function in patients treated with PCSK9 inhibitors (PCSK9i). This is the first analysis: (1) discussion about the role of the Hospital Pharmacists during the pandemic, and also the assessment of the impact of COVID-19 in the lipid control; (2) descriptive analysis; (3) effectiveness in LDL cholesterol (LDL-c) reduction of alirocumab and evolocumab; (4) communicate PCSK9i safety.

Material and methods: It is a prospective Real-World Evidence analysis of patients that take PCSK9i for the first time in the usual clinical practice, and they are included after the first dispensation in the public pharmacy consultations of 12 Hospitals in Galicia from May 2020 to April 2021. Baseline values of LDL-c are the previous values before taking PCSK9 and the follow-up values are in 6 months time.

Results: 89 patients were included. 86.5% with cardiovascular disease and 53.9% with statin intolerances. 78.8% of the patients were treated with high intensity statins. Statins most used were rosuvastatin (34.1%) and atorvastatin (20.5%). Baseline value of LDL-c was 148mg/dL and the follow-up value was 71mg/dL. The baseline value of patients treated with alirocumab (N=43) was 144mg/dL and 73mg/dL in the follow-up. With evolocumab (N=46) was 151mg/dL in basaline and 69mg/dL in follow-up. The LDLc- reduction was 51.21% with evolocumab and 51.05% with alirocumab. 43.1% of the patients showed values >70mg/dL in six month time; 19.4% between 69mg/dl and 55mg/dL and 37.5% <55mg/dL. 58.3% of the patients achieved a reduction >50% of LDL-c. The adverse events were: injection point reaction (N=2), myalgias (N=1), flu-like symptoms (N=1) and neurocognitive worsening (N=1).

Conclusions: (1) Despite the number of prescriptions was reduced because of the pandemic, the lipid control was not affected. (2) Half of the patients treated with PSCK9i is due to statins intolerance and the 86% is for secondary prevention. (2) The reduction results were similar to pivotal clinical trials. Despite this, 39% of the total of the patients and 60% of patients with dual teraphy did not reach the goal of ESC/EAS guidelines (<55mg/dL and/or reduction>50%). There were not significant differences between evolocumab and alirocumab: 51.21% vs 51.05% (P=.972). (3) There were not any adverse events of special interest. The possible neurocognitive worsening will be studied as the primary endpoint once the MEMOGAL study has been completed.

Keywords: COVID-19; Colesterol-LDL; Effectiveness-safety; Eficacia-seguridad; Inhibidores de la PCSK9; LDL-cholesterol; PCSK9 inhibitors.

Copyright © 2022 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Figures

Figura 1
Figura 1
Inclusión de pacientes y casos de COVID-19 en hospitales gallegos.
Figura 2
Figura 2
Nivel basal de LDL y al seguimiento.

References

    1. Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., 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;38:2459–2472. doi: 10.1093/eurheartj/ehx144.
    1. Grundy S.M., Stone N.J., Bailey A.L., Beam C., Birtcher K.K., Blumenthal R.S., et al. 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. 2019;73:e285–e350. doi: 10.1016/j.jacc.2018.11.003.
    1. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Eur Heart J. 2020;41:111–188. doi: 10.1093/eurheartj/ehz455.
    1. Lloyd-Jones D.M., Morris P.B., Ballantyne C.M., Birtcher K.K., Daly D.D., Jr., DePalma S.M., et al. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70:1785–1822. doi: 10.1016/j.jacc.2017.07.745.
    1. Sabatine M.S., Giugliano R.P., Wiviott S.D., Raal F.J., Blom D.J., Robinson J., et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500–1509. doi: 10.1056/NEJMoa1500858.
    1. Robinson J.G., 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;372:1489–1499. doi: 10.1056/NEJMoa1501031.
    1. World Helath Organitation WHO Director-General's remarks at the media briefing on 2019-nCoV on 11 February. 2020 Disponible en: .
    1. Choudry F.A., Hamshere S.M., Rathod K., Akhtar M.M., Archbold A.R., et al. High thrombus burden in patients with COVID-19 presenting with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2020;76:1168–1176. doi: 10.1016/j.jacc.2020.07.022.
    1. Seijas-Amigo J., Rodríguez-Penas D., Estany-Gestal A., Suárez-Artime P., Santamaría-Cadavid M., et al. Observational multicentre prospective study to assess changes in cognitive function in patients treated with PCSK9i. Study protocol. Farm Hosp. 2021;45:150–154. doi: 10.7399/fh.11569.
    1. Robinson J.G., Colhoun H.M., Bays H.E., Jones P.H., Du Y., Hanotin C., et al. Efficacy and safety of alirocumab as add-on therapy in high cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): Design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol. 2014;37:597–604. doi: 10.1002/clc.22327.
    1. Rodriguez-Escobedo R., Gonzalez-Martinez S., Díaz-Naya L., Suarez-Gutierrez L., Fernández-Morera J., et al. Real-life efficacy and safety of PCSK9 inhibitors treatment: Experience in three hospital in Asturias. Semergen. 2021;47:369–375. doi: 10.1016/j.semerg.2021.03.008.
    1. Kastelein J.J., Hovingh G.K., Langslet G., Baccara-Dinet M.T., Gipe D.A., Chaudhari U., et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017;11:195–203. doi: 10.1016/j.jacl.2016.12.004. e4.
    1. Gitt A.K., Lautsch D., Ferrieres J., De Ferrari G.M., Vyas A., Baxter C.A., et al. Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: Results from the Dyslipidemia International Study II. Atherosclerosis. 2017;266:158–166. doi: 10.1016/j.atherosclerosis.2017.08.013.
    1. Ley 3/2019, de 2 de julio, de ordenación farmacéutica de Galicia. Disponible en:
    1. Ollendorf J.D.A., Pearson S.D., Tice J.A., Guzman D., Bibbins-Domingo K. Cost-effectiveness of PCSK9 Inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. JAMA. 2016;316:743–753. doi: 10.1001/jama.2016.11004.
    1. Fonarow G.C., Keech A.C., Pedersen T.R., Giugliano R.P., Sever P.S., Lindgren P., et al. Cost-effectiveness of evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. 2017;2:1069–1078. doi: 10.1001/jamacardio.2017.2762.
    1. Ruiz-Romero V., Martinez Pillado M., Torres-Domínguez Y., Acón-Royo D., De Toro-Salas., et al. Evaluación de la satisfacción del paciente en la teleconsulta durante la pandemia por COVID-19. Rev Esp Salud Pública. 2021;95 e1-11.
    1. Anguita Sánchez M.B., Gómez Doblas J.J., Barrios Alonso V. Grado de control del cLDL tras un síndrome coronario agudo en España. ¿Se utilizan adecuadamente los recursos terapéuticos existentes? Rev Esp Cardiol. 2021;74:194–196. doi: 10.1016/j.recesp.2020.06.011.
    1. Galve E., Cordero A., Cequier A., Ruiz E., Gonzalez-Juanatey J.R. Grado de control lipídico en pacientes coronarios y medidas adoptadas por los médicos Estudio REPAR. Rev Esp Cardiol. 2016;69:931–938. doi: 10.1016/j.recesp.2016.02.013.
    1. Reiner Z., de Backer G., Fras Z., Kotseva K., Tokgözoglu L., Wood D., 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.
    1. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Eur Heart J. 2020;41:111–188. doi: 10.1093/eurheartj/ehz455.
    1. Seijas Amigo J., Rodríguez-Mañero M., Cordero A., Ibarrondo O., Itziar Oyagüez J.M., et al. Análisis restrospectivo del grado de control lipídico y eventos coronarios en prevención secundaria en pacientes en vida real. Rev Esp Cardiol. 2020;73(Supl 1):189. Disponible en: .
    1. Kotseva K., de Backer G., de Bacquer D., Arno Hoes L.R., et al. Eur J Prev Cardiol 2019. Int J Cardiol. 2018;258:1–6. DOI: 10.1177/2047487318825350.
    1. Stein E.A., Honarpour N., Wasserman S.M., Xu F., Scott R., Raal F.J. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013;128:2113–2120. DOI: 10.1161/CIRCULATIONAHA.113.004678.
    1. Moriarty P.M., Parhofer K.G., Babirak S.P., Cornier M.A., Duell P.B., et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016;37:3588–3595. doi: 10.1093/eurheartj/ehw388.
    1. Sabatine M.S., Giugliano R.P., 402 Wiviott S.D., Raal F.J., Blom D.J., et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500–1509. doi: 10.1056/NEJMoa1500858.
    1. Giugliano R.P., Mach F., Zavitz K., Kurtz C., Im K., et al. Cognitive function in a randomized trial of evolocumab. N Engl J Med. 2017;377:633–643. doi: 10.1056/NEJMoa1701131.
    1. Ray K.K., et al. Safety and efficacy of bempedoic acid to reduce LDL colesterol. CLEAR Harmony Trial. N Engl J Med. 2019;380:1022–1103.
    1. Goldberg A.C., Leiter L.A., Erik S.G., Stroes M.D., et al. Effect of bempedoic acid vs placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019;322:1780–1788. doi: 10.1001/jama.2019.16585.
    1. González-Juanatey J.R., Rey-Aldana D., Cinza-Sanjurjo S., Portela-Romero M., López-Barreiro J.L., et al. Programa de consulta electrónica universal (e-consulta) de un servicio de cardiología. Resultados a largo plazo. Rev Esp Cardiol. 2020 doi: 10.1016/j.recesp.2020.11.007.

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