Advance Search

LDL-cholesterol goal attainment with ezetimibe and bempedoic acid in patients at high and very-high cardiovascular risk: A simulation study in the Italian cohort of the SANTORINI study

A simulation study in the SANTORINI Italian cohort

Marcello Arca
Department of Translational and Precision Medicine, “Sapienza”, University of Rome, Rome, Italy
Angela Pirillo
Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy
Rosanna Gambacurta
Daiichi Sankyo Italia S.p.A., Medical Affairs, Rome, Italy
Christian Becker
Daiichi Sankyo Europe GmbH, Munich, Germany
Françoise Diamand
Daiichi Sankyo Europe GmbH, Munich, Germany
Kausik K Ray
Imperial Centre for Cardiovascular Disease Prevention, ICTU-Global, Imperial College London, London, United Kingdom
Alberico L. Catapano
IRCCS MultiMedica, Milan, Italy, and Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
Keywords:
Copyright and Licensing:

Copyright (c) 2024 European Atherosclerosis Journal

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Abstract

Aims: Data from the Italian cohort of the SANTORINI study, a European observational study focusing on lipid management in patients at high or very-high cardiovascular risk, were used to simulate the effect of sequential addition of ezetimibe and bempedoic acid in patients not at LDL-C goal with their current lipid-lowering therapy (LLT).
Methods: Eligible patients were selected based on criteria including LDL-C levels and LLT status. Patients who were not at LDL-C goal at baseline and had not received PCSK9 inhibitors (PCSK9i) or bempedoic acid underwent sequentially 1) simulation of adding ezetimibe in patients who had not previously received this drug, and 2) simulation of the effect of adding bempedoic acid in patients who did not achieve the LDL-C goal after treatment with ezetimibe (actual or simulated). Expected treatment efficacy was documented from randomised clinical trials. The simulation assumed no statin intensification beyond the baseline regimen. The simulation was run probabilistically 10,000 times for the patient cohort, calculating the mean LDL-C after each simulation step and estimating the proportion of patients achieving LDL-C goal at each stage and overall.
Results: The simulation resulted in a significant increase in patients achieving the LDL-C goal after each step (from 25.9% to 37.6% after ezetimibe and 55.4% after ezetimibe+bempedoic acid). The subgroup analysis showed similar trends in high-risk and very-high-risk patients.
Conclusions: The simulation of SANTORINI data shows that goal attainment in patients at high-risk and very-high-risk can be substantially increased by optimizing oral LLT with the addition of ezetimibe and bempedoic acid.

This is the update version of the article. A correction has been published:
EAJ 2024;3:93 - https://doi.org/10.56095/eaj.v3i3.86

Updated PDF Article and Supplementary Material
Supplementary Material
Updated PDF Article and Supplementary Material
Supplementary Material

Article Metrics Graph

Article Views | PDF Downloads
Chart Graph | Range Graph

References

  1. Pirillo A, Norata GD. The burden of hypercholesterolemia and ischemic heart disease in an ageing world. Pharmacol Res 2023; 193:106814. https://doi.org/10.1016/j.phrs.2023.106814
  2. Mensah GA, Fuster V, Murray CJL, et al. Global Burden of Cardiovascular Diseases and Risks, 1990-2022. J Am Coll Cardiol 2023; 82:2350-473. https://doi.org/10.1016/j.jacc.2023.11.007
  3. 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; 38:2459-72. https://doi.org/10.1093/eurheartj/ehx144
  4. 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; 41:2313-30. https://doi.org/10.1093/eurheartj/ehz962
  5. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41:111-88. https://doi.org/10.1093/eurheartj/ehz455
  6. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016; 37:2999-3058. https://doi.org/10.1093/eurheartj/ehw272
  7. De Backer G, Jankowski P, Kotseva K, 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. https://doi.org/10.1016/j.atherosclerosis.2019.03.014
  8. Ray KK, Molemans B, Schoonen WM, 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. https://doi.org/10.1093/eurjpc/zwaa047
  9. Landmesser U, Pirillo A, Farnier M, et al. Lipid-lowering therapy and low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: The ACS patient pathway project. Atheroscler Suppl 2020; 42:e49-e58. https://doi.org/10.1016/j.atherosclerosissup.2021.01.009
  10. Ray KK, Haq I, Bilitou A, et al. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study. Lancet Reg Health Eur 2023; 29:100624. https://doi.org/10.1016/j.lanepe.2023.100624
  11. Arca M, Calabrò P, Solini A, et al. Lipid-lowering treatment and LDL-C goal attainment in high and very high cardiovascular risk patients: Evidence from the SANTORINI study-The Italian experience. Eur Ath J 2023; 2:1-13. https://doi.org/10.56095/eaj.v2I1.26
  12. Ballantyne CM, Bays H, Catapano AL, et al. Role of Bempedoic Acid in Clinical Practice. Cardiovasc Drugs Ther 2021; 35:853-64. https://doi.org/10.1007/s10557-021-07147-5
  13. Nissen SE, Lincoff AM, Brennan D, et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med 2023; 388:1353-64. https://doi.org/10.1056/NEJMoa2215024
  14. Cannon CP, Khan I, Klimchak AC, et al. Simulation of Lipid-Lowering Therapy Intensification in a Population With Atherosclerotic Cardiovascular Disease. JAMA Cardiol 2017; 2:959-66. https://doi.org/10.1001/jamacardio.2017.2289
  15. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372:2387-97. https://doi.org/10.1056/NEJMoa1410489
  16. Descamps O, Tomassini JE, Lin J, et al. Variability of the LDL-C lowering response to ezetimibe and ezetimibe + statin therapy in hypercholesterolemic patients. Atherosclerosis 2015; 240:482-9. https://doi.org/10.1016/j.atherosclerosis.2015.03.004
  17. Goldberg AC, Leiter LA, Stroes ESG, 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; 322:1780-8. https://doi.org/10.1001/jama.2019.16585
  18. Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med 2019; 380:1022-32. https://doi.org/10.1056/NEJMoa1803917
  19. Laufs U, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J Am Heart Assoc 2019; 8:e011662. https://doi.org/10.1161/JAHA.118.011662
  20. Ballantyne CM, Banach M, Mancini GBJ, et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis 2018; 277:195-203. https://doi.org/10.1016/j.atherosclerosis.2018.06.002
  21. Agenzia Italiana del Farmaco. DETERMINA n. 435/2022. GU n.138 del 15-6-2022. https://www.aifa.gov.it/documents/20142/961234/Determina_435-2022_Repatha.pdf
  22. Agenzia Italiana del Farmaco. DETERMINA n. 434/2022. GU n.138 del 15-6-2022. https://www.aifa.gov.it/documents/20142/961234/Determina_434-2022_Praluent.pdf
  23. Yu M, Liang C, Kong Q, et al. Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: a meta-analysis of literature. Lipids Health Dis 2020; 19:1. https://doi.org/10.1186/s12944-019-1182-5
  24. Bays HE. Cholesterol-lowering drugs: Focus on Ezetimibe. Eur Ath J 2022; 1:14-24. https://doi.org/10.56095/eaj.v1i1.8
  25. Brennan S, Mc Evoy JW. Bempedoic acid and PCSK9 inhibitor eligibility in a contemporary population with atherosclerotic cardiovascular disease. Eur J Prev Cardiol 2022; 29:zwac056.165. https://doi.org/10.1093/eurjpc/zwac056.165
  26. Katzmann JL, Becker C, Bilitou A, Laufs U. Simulation study on LDL cholesterol target attainment, treatment costs, and ASCVD events with bempedoic acid in patients at high and very-high cardiovascular risk. PLoS One 2022; 17:e0276898. https://doi.org/10.1371/journal.pone.0276898

Send mail to Author

Send Cancel

Custom technologies based on your needs

  • MongoDB
  • ElasticSearch
  • Redis
  • Solr
  • Memcached