Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose–response model

Title
Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose–response model
Publication Date
2022-10
Author(s)
Jadhav, Satyawan B
Crass, Ryan L
Chapel, Sunny
Kerschnitzki, Michael
Sasiela, William J
Emery, Maurice G
Amore, Benny M
Barrett, P Hugh R
( author )
OrcID: https://orcid.org/0000-0003-3223-6125
Email: pbarret6@une.edu.au
UNE Id une-id:pbarret6
Watts, Gerald F
Catapano, Alberico L
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
Oxford University Press
Place of publication
The United Kingdom
DOI
10.1093/ehjcvp/pvab064
UNE publication id
une:1959.11/56295
Abstract

Aims Many patients are unable to achieve guideline-recommended LDL cholesterol (LDL-C) targets, despite taking maximally tolerated lipid-lowering therapy. Bempedoic acid, a competitive inhibitor of ATP citrate lyase, significantly lowers LDL-C with or without background statin therapy in diverse populations. Because pharmacodynamic interaction between statins and bempedoic acid is complex, a dose-response model was developed to predict LDL-C pharmacodynamics following administration of statins combined with bempedoic acid.

Methods And Results Bempedoic acid and statin dosing and LDL-C data were pooled from 14 phase 1-3 clinical studies. Dose-response models were developed for bempedoic acid monotherapy and bempedoic acid-statin combinations using previously published statin parameters. Simulations were performed using these models to predict change in LDL-C levels following treatment with bempedoic acid combined with clinically relevant doses of atorvastatin, rosuvastatin, simvastatin, and pravastatin. Dose-response models predicted that combining bempedoic acid with the lowest statin dose of commonly used statins would achieve a similar degree of LDL-C lowering as quadrupling that statin dose" for example, the predicted LDL-C lowering was 54% with atorvastatin 80 mg compared with 54% with atorvastatin 20 mg + bempedoic acid 180 mg, and 42% with simvastatin 40 mg compared with 46% with simvastatin 10 mg + bempedoic acid 180 mg.

Conclusion These findings suggest bempedoic acid combined with lower statin doses offers similar LDL-C lowering compared with statin monotherapy at higher doses, potentially sparing patients requiring additional lipid-lowering therapies from the adverse events associated with higher statin doses.

Link
Citation
European Heart Journal- Cardiovascular Pharmacotherapy, 8(6), p. 578-586
ISSN
2055-6845
2055-6837
Start page
578
End page
586
Rights
Attribution-NonCommercial 4.0 International

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