Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study.

Background: The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study.
Methods: Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed.
Findings: In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) ( n  = 962), 27.0% ( n  = 259) and 57.0% ( n  = 548 ) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD ( n  = 74), 88.1% ( n  = 65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD ( n  = 1520), 12.0% ( n  = 183), 42.1% ( n  = 641) and 93.2% ( n  = 1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively.
Interpretation: Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk.
Funding: Amgen.
Competing Interests: JB has received speaker fees from Amgen and research grant support from AstraZeneca. SB is an employee of Amgen Ltd and holds stock in Amgen. GV is an employee of Amgen (Europe) GmbH and holds stock in Amgen. ALC has received research grant(s)/support from Amgen, Eli Lilly, Menarini, Mylan, Sanofi, and Sanofi-Regeneron; and has served as a consultant for or received fees from Aegerion, Akcea, Amgen, Amryt, AstraZeneca, Daiichi Sankyo, Esperion, Genzyme, Ionis Pharmaceuticals, Kowa, Medco, Menarini, MSD, Mylan, Novartis, Recordati, Regeneron, and Sanofi. NP has received consultancy fees and financial support for research projects from Amgen and Pfizer, and financial support for arranging and speaking at educational meetings from Amgen, MSD and Pfizer. He holds no stocks and shares in any such companies. NP is supported by the National Institute for Health Research Senior Investigator Awards, Biomedical Research Centre funding, and the British Heart Foundation Research Centre Excellence Award. He has received financial support from several pharmaceutical companies which manufacture lipid lowering agents, for consultancy fees (Pfizer and Amgen), research projects and staff (Pfizer and Amgen) and for arranging and speaking at educational meetings (MSD, Amgen and Pfizer). He holds no stocks and shares in any such companies. AJV-V has participated, or is currently participating, in research grants to Imperial College London from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron, and Sanofi-Aventis; has received personal fees for consulting from Bayer and Regeneron; and has received fees for lectures from Akcea, Amgen, Mylan and Ferrer; all outside the submitted work. KKR reports grants from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron and Sanofi; and has received personal fees from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Beren Therapeutics, Biologix Pharma, Boehringer Ingelheim, Cargene, CSL Behring, CRISPR, Eli Lilly Esperion, Kowa, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Silence Therapeutics, SCRIBE Therapeutics, Vaxxinity and Viatris.
(© 2023 The Author(s).)