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
Watts, Gerald F
Catapano, Alberico L
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Publication Date |
2022-10
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Abstract |
<p><b>Aims</b> 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.</p> <p><b>Methods And Results</b> 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.</p> <p><b>Conclusion</b> 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.</p>
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Citation |
European Heart Journal- Cardiovascular Pharmacotherapy, 8(6), p. 578-586
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ISSN |
2055-6845
2055-6837
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Link | |
Publisher |
Oxford University Press
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Rights |
Attribution-NonCommercial 4.0 International
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Title |
Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose–response model
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Type of document |
Journal Article
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Entity Type |
Publication
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Name | Size | format | Description | Link |
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openpublished/PharmacodynamicBarret2022JournalArticle.pdf | 691.009 KB | application/pdf | Published Version | View document |