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. 2023 Jul;135(13-14):364-374.
doi: 10.1007/s00508-023-02221-4. Epub 2023 Jun 8.

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients

Hermann Toplak  1 , Aikaterini Bilitou  2 , Hannes Alber  3 , Johann Auer  4 , Martin Clodi  5   6 , Christoph Ebenbichler  7 , Evelyn Fließer-Görzer  8 , Carmen Gelsinger  9 , Ursula Hanusch  10 , Bernhard Ludvik  11 , Thomas Maca  12 , Andreas Schober  13 , Reinhard Sock  14 , Walter S Speidl  15 , Thomas M Stulnig  16 , Raimund Weitgasser  17 , Andreas Zirlik  18 , Marina Koch  19 , Sebastian Wienerroither  19 , Sorrel E Wolowacz  20 , Françoise Diamand  21 , Alberico L Catapano  22
Affiliations

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients

Hermann Toplak et al. Wien Klin Wochenschr. 2023 Jul.

Abstract

Objective: The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe a real-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals.

Methods: Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type 9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using a Monte Carlo simulation.

Results: A cohort of patients (N = 144) with a mean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with a decrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall.

Conclusions: The SANTORINI real-world data in Austria suggest that a proportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

Keywords: Atherosclerosis; Bempedoic acid; Cardiovascular; ComBination therapy; Ezetimibe; Lipid lowering therapy.

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Conflict of interest statement

C. Gelsinger, T. Maca, R. Sock declare that they have no competing interests. S. Wolowacz is an employee of RTI Health Solutions. RTI Health Solutions received funding from Daiichi Sankyo Europe GmbH for the preparation of this manuscript. A. Bilitou, M. Koch, S. Wienerroither, and F. Diamand are employees of Daiichi Sankyo. Daiichi Sankyo Europe GmbH is the market authorisation holder in Europe, Switzerland, and the United Kingdom for bempedoic acid and bempedoic acid fixed-dose combination with ezetimibe. All co-authors received study fees from Daiichi Sankyo. H. Toplak has received honoraria for lecturing and consulting as well as research support from Daiichi Sankyo. H. Alber has received study fees from Daiichi Sankyo, and lecture and consulting fees from Daiichi Sankyo, Novartis, Amgen, and Sanofi-Aventis. J. Auer has received consulting work and lecture fees from Novartis, Amgen, Sanofi, and Daiichi Sankyo. M. Clodi has received lecture and consultant fees from Astra Zeneca, Boerhinger Ingelheim, Novo Nordisk, Novartis, Sanofi, Amgen, and Daiichi Sankyo. C. Ebenbichler has received grants and personal fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Novartis, NovoNordisk, Sanofi, and Sobi. E. Fließer-Görzer has received presentation, study, and/or congress support from Novo Nordisk, AstraZeneca, Bristol-Myers Squibb, Bayer, Novartis, Eli Lilly, Allergan, Daiichi Sankyo, Amgen, Merck Sharpe & Dohme, Boehringer Ingelheim, and Sanofi Aventis. U. Hanusch has acted as investigator in clinical trials conducted by Bayer, Lilly, Amgen, Vertanical, and Novo Nordisk. B. Ludvik has received honoraria for lectures, advisory boards, and research support from Amgen, Sanofi, Novartis, and Daiichi Sankyo. A. Schober has received speaker fees and institutional research support from Daiichi-Sankyo. W. Speidl has received support for lectures, advisory board participation, clinical trials, and/or other research from Amgen, Daiichi Sankyo, Novartis, and Sanofi. T. Stulnig has received honoraria for lectures and/or consultation as well as travel support from Amgen, Daiichi-Sankyo, Novartis, Sanofi, Sobi; research support from Daiichi-Sankyo and Sanofi. R. Weitgasser has received research grants, speaker fees, and consultant advisory board fees (2017–2022) from the following: Abbott Diabetes Care, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Medtrust, Merck Sharp & Dohme, Novo Nordisk, Roche Diabetes Care, Sanofi, and Spar. A. Zirlik has received consultant fees from Bayer Health Care, Boehringer Ingelheim, Rigel, Cardiorentis, Medscape Stealth Peptides, Sanofi Aventis, Medtronic, Norvatis and honoraria for lectures from Bayer Health Care, Astra Zeneca, Medtronic, ResMed, Boehringer Ingelheim, Rigel, Sanofi Aventis, Pfizer, Janssen-Cilag, Novartis, Bristol Myers Squibb, Thoratec, Abiomed, Daiichi Sankyo, Abbott and Cardiac Dimensions. A.L. Catapano has received honoraria, lecture fees, or research grants from the following: Amarin, Sigma-Tau, Menarini, Kowa, Recordati, Eli Lilly, AstraZeneca, Mediolanum, Pfizer, Merck, Sanofi, Aegerion, Amgen, Genzyme, Bayer, Sanofi, Regeneron, Daiichi Sankyo, and The Corpus. The work of A.L. Catapano is supported in part by the Italian Ministry of Health—Ricerca Corrente.

Figures

Fig. 1
Fig. 1
Representation of the simulation algorithm in the LLT pathway (LDL‑C low-density lipoprotein cholesterol, LLT lipid-lowering therapy)
Fig. 2
Fig. 2
Treatment effects for bempedoic acid in patients receiving: a moderate or high-dose statin, Pooled Patient-Level Data from CLEAR Harmony and CLEAR Wisdom (Pool 1); n = 1922; b no or low-dose statin as background therapy, Pooled Patient-Level Data from CLEAR Serenity and CLEAR Tranquility (Pool 2); n = 399. Green bars represent the patient distribution for the ratio of LDL‑C at week 12 versus LDL‑C at baseline observed in the pooled CLEAR trial data. The blue curves represent the fitted lognormal distributions (LDL‑C low-density lipoprotein cholesterol)
Fig. 3
Fig. 3
Comparison of physician-reported versus calculated CV risk using the ESC/EAS classification (a) and goal attainment overall and by CV risk (b) in the simulation cohort. CV risk was calculated as per the risk classification reported in ESC/EAS 2019 guidelines. LDL‑C goal attainment was determined according to the ESC/EAS 2019 recommendations (CV cardiovascular, EAS European Atherosclerosis Society, ESC European Society for Cardiology)
Fig. 4
Fig. 4
Results of the lipid-lowering therapy intensification simulation in the cohort (N = 144) (BA bempedoic acid, LDL‑C low-density lipoprotein cholesterol)
Fig. 5
Fig. 5
LDL‑C distribution at baseline and after lipid-lowering therapy intensification: a LDL‑C distribution at baseline, b LDL‑C distribution after the treatment simulation
See this image and copyright information in PMC

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