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Neue Optionen zur Intensivierung der lipidsenkenden Therapie

Rolle von Bempedoinsäure in der Kombinationstherapie

Novel options to maximize oral lipid lowering treatment

Role of bempedoic acid in combination treatment

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Zusammenfassung

Epidemiologische, randomisierte, kontrollierte, klinische und genetische Studien belegen, dass das LDL(„low-density lipoprotein“)-Cholesterin (LDL-C) einen ursächlichen Faktor für atherosklerotische Erkrankungen darstellt. Die aktuellen ESC/EAS-Leitlinien zum Management von Dyslipidämien empfehlen für Hochrisikopatienten einen LDL-C-Zielwert von weniger als 55 mg/dl und eine mindestens 50 %ige Reduktion des LDL-C-Ausgangswertes. Leider werden diese Zielwerte im klinischen Alltag häufig nicht erreicht, wie auch jüngste Studiendaten aus EUROASPIRE oder DaVinci belegen. Daher sind Kombinationstherapien empfohlen, die, wie auch bei der Blutdrucktherapie, den Therapieerfolg verbessern können. Bempedoinsäure ist eine neue Substanz, die für eine Kombinationstherapie geeignet ist und insbesondere für Patienten mit statinassoziierten Muskelsymptomen eine Alternative darstellt und den LDL-C-Wert bei statinnaiven Patienten um etwa 25 %, zusätzlich zu Statinen um etwa 18 % senkt. In einer Fixdosiskombination mit Ezetimib kann bei statinnaiven Patienten eine LDL-C-Senkung um bis zu 45 %, zusätzlich zu Statinen um 38 % (placebokorrigiert) erreicht werden. Bempedoinsäure ist in der Regel sehr gut verträglich, kann allerdings zu einem reversiblen Anstieg der Harnsäure führen. Gelegentlich wurde eine leichte Abnahme des Hämoglobins dokumentiert. Daher wird empfohlen, in den ersten 3 Monaten nicht nur die Veränderungen der Lipidwerte, sondern auch Harnsäure und hämatologische Parameter zu kontrollieren.

Abstract

Epidemiological, randomized, controlled, clinical and genetic studies confirm that low-density lipoprotein cholesterol (LDL-C) is a causative factor for atherosclerotic diseases. The current European Society of Cardiology and European Atherosclerosis Society (ESC/EAS) guidelines on the management of dyslipidemia recommend a target LDL-C < 55 mg/dl and at least a 50% reduction in baseline LDL‑C for high-risk patients; however, these target values are often not achieved in routine clinical practice, as shown by recent cross-sectional data from EUROASPIRE or DaVinci. Therefore, combination treatment is recommended, which, as with treatment of blood pressure, can improve the success of treatment. Bempedoic acid is a new substance, which is suitable for combination treatment and represents an alternative particularly for patients with statin-associated muscular symptoms. Bempedoic acid reduces LDL‑C by approximately 25% in statin-naïve patients and by some 18% in addition to statins. In a fixed doses combination with ezetimibe, bempedoic acid can lower LDL‑C by up to 45% in statin-naïve patients and by 38% (placebo-corrected) in addition to statins. Bempedoic acid is generally very well tolerated: however, it can lead to a reversible increase in uric acid. Occasionally, a slight decrease in hemoglobin has been documented. Therefore, it is recommended that not only changes in lipid levels but also uric acid and hematological parameters should be monitored in the first 3 months.

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Literatur

  1. Ference BA, Ginsberg HN, Graham I et al (2017) 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 38:2459–2472. https://doi.org/10.1093/eurheartj/ehx144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Di Angelantonio E, Gao P, Pennells L et al (2012) Lipid-related markers and cardiovascular disease prediction. JAMA 307:2499–2506. https://doi.org/10.1001/jama.2012.6571

    Article  CAS  PubMed  Google Scholar 

  3. Lewington S, Whitlock G, Clarke R et al (2007) Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 370:1829–1839. https://doi.org/10.1016/S0140-6736(07)61778-4

    Article  CAS  PubMed  Google Scholar 

  4. Borén J, Chapman MJ, Krauss RM et al (2020) 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 41:2313–2330. https://doi.org/10.1093/eurheartj/ehz962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Baigent C, Blackwell L, Emberson J et al (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376:1670–1681. https://doi.org/10.1016/S0140-6736(10)61350-5

    Article  CAS  PubMed  Google Scholar 

  6. Sabatine MS, Giugliano RP, Keech AC et al (2017) Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 376:1713–1722. https://doi.org/10.1056/NEJMoa1615664

    Article  CAS  PubMed  Google Scholar 

  7. Schwartz GG, Steg PG, Szarek M et al (2018) Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 379:2097–2107. https://doi.org/10.1056/NEJMoa1801174

    Article  CAS  PubMed  Google Scholar 

  8. Cannon CP, Blazing MA, Giugliano RP et al (2015) Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 372:2387–2397. https://doi.org/10.1056/NEJMoa1410489

    Article  CAS  PubMed  Google Scholar 

  9. Ference BA (2015) Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps. Curr Opin Lipidol 26:566–571. https://doi.org/10.1097/MOL.0000000000000247

    Article  CAS  PubMed  Google Scholar 

  10. Holmes MV, Asselbergs FW, Palmer TM et al (2015) Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J 36:539–550. https://doi.org/10.1093/eurheartj/eht571

    Article  CAS  PubMed  Google Scholar 

  11. Giugliano RP, Pedersen TR, Park J‑G et al (2017) Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet 390:1962–1971. https://doi.org/10.1016/S0140-6736(17)32290-0

    Article  CAS  PubMed  Google Scholar 

  12. Giugliano RP, Mach F, Zavitz K et al (2017) Cognitive function in a randomized trial of evolocumab. N Engl J Med 377:633–643. https://doi.org/10.1056/NEJMoa1701131

    Article  CAS  PubMed  Google Scholar 

  13. Gencer B, Mach F, Guo J et al (2020) Cognition after lowering LDL-cholesterol with evolocumab. J Am Coll Cardiol 75:2283–2293. https://doi.org/10.1016/j.jacc.2020.03.039

    Article  CAS  PubMed  Google Scholar 

  14. Harvey PD, Sabbagh MN, Harrison JE et al (2018) No evidence of neurocognitive adverse events associated with alirocumab treatment in 3340 patients from 14 randomized phase 2 and 3 controlled trials: a meta-analysis of individual patient data. Eur Heart J 39:374–381. https://doi.org/10.1093/eurheartj/ehx661

    Article  CAS  PubMed  Google Scholar 

  15. Karagiannis AD, Mehta A, Dhindsa DS et al (2021) How low is safe? The frontier of very low (〈30 mg/dL) LDL cholesterol. Eur Heart J 42:2154–2169. https://doi.org/10.1093/eurheartj/ehaa1080

    Article  CAS  PubMed  Google Scholar 

  16. Ballantyne CM, Raichlen JS, Nicholls SJ et al (2008) Effect of rosuvastatin therapy on coronary artery stenoses assessed by quantitative coronary angiography: a study to evaluate the effect of rosuvastatin on intravascular ultrasound-derived coronary atheroma burden. Circulation 117:2458–2466. https://doi.org/10.1161/CIRCULATIONAHA.108.773747

    Article  CAS  PubMed  Google Scholar 

  17. Nicholls SJ, Puri R, Anderson T et al (2016) Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA 316:2373–2384. https://doi.org/10.1001/jama.2016.16951

    Article  CAS  PubMed  Google Scholar 

  18. Nicholls SJ, Nissen SE, Prati F et al (2021) Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study. Cardiovasc Diagn Ther 11:120–129. https://doi.org/10.21037/cdt-20-684

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ference BA, Yoo W, Alesh I et al (2012) Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol 60:2631–2639. https://doi.org/10.1016/j.jacc.2012.09.017

    Article  CAS  PubMed  Google Scholar 

  20. Zhang Y, Pletcher MJ, Vittinghoff E et al (2021) Association between cumulative low-density lipoprotein cholesterol exposure during young adulthood and middle age and risk of cardiovascular events. JAMA Cardiol 6:1406–1413. https://doi.org/10.1001/jamacardio.2021.3508

    Article  PubMed  Google Scholar 

  21. Mach F, Baigent C, Catapano AL et al (2020) 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 41:111–188. https://doi.org/10.1093/eurheartj/ehz455

    Article  PubMed  Google Scholar 

  22. Ray KK, Molemans B, Schoonen WM et al (2021) EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study. Eur J Prev Cardiol 28:1279–1289. https://doi.org/10.1093/eurjpc/zwaa047

    Article  PubMed  Google Scholar 

  23. De Backer G, Jankowski P, Kotseva K et al (2019) Management of dyslipidaemia in patients with coronary heart disease: results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis 285:135–146. https://doi.org/10.1016/j.atherosclerosis.2019.03.014

    Article  CAS  PubMed  Google Scholar 

  24. Atkins ER, Chow CK (2020) Low-dose combination therapy for initial treatment of hypertension. Curr Hypertens Rep 22:65. https://doi.org/10.1007/s11906-020-01069-7

    Article  PubMed  Google Scholar 

  25. Bennett A, Chow CK, Chou M et al (2017) Efficacy and safety of quarter-dose blood pressure-lowering agents: a systematic review and meta-analysis of randomized controlled trials. Hypertension 70:85–93. https://doi.org/10.1161/HYPERTENSIONAHA.117.09202

    Article  CAS  PubMed  Google Scholar 

  26. Chow CK, Atkins ER, Billot L et al (2021) Ultra-low-dose quadruple combination blood pressure-lowering therapy in patients with hypertension: the QUARTET randomized controlled trial protocol. Am Heart J 231:56–67. https://doi.org/10.1016/j.ahj.2020.09.017

    Article  CAS  PubMed  Google Scholar 

  27. Katzmann JL, Sorio-Vilela F, Dornstauder E et al (2020) Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL‑C. Clin Res Cardiol. https://doi.org/10.1007/s00392-020-01740-8

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rubino J, MacDougall DE, Sterling LR et al (2021) Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: a randomized clinical trial. Atherosclerosis 320:122–128. https://doi.org/10.1016/j.atherosclerosis.2020.12.023

    Article  CAS  PubMed  Google Scholar 

  29. Ballantyne CM, Bays H, Catapano AL et al (2021) Role of bempedoic acid in clinical practice. Cardiovasc Drugs Ther 35:853–864. https://doi.org/10.1007/s10557-021-07147-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Brandts J, Ray KK (2020) Bempedoic acid, an inhibitor of ATP citrate lyase for the treatment of hypercholesterolemia: early indications and potential. Expert Opin Investig Drugs 29:763–770. https://doi.org/10.1080/13543784.2020.1778668

    Article  CAS  PubMed  Google Scholar 

  31. Wichaiyo S, Supharattanasitthi W (2021) Bempedoic acid: a new non-statin drug for the treatment of dyslipidemia. Clin Drug Investig 41:843–851. https://doi.org/10.1007/s40261-021-01075-w

    Article  CAS  PubMed  Google Scholar 

  32. Ray KK, Bays HE, Catapano AL et al (2019) Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med 380:1022–1032. https://doi.org/10.1056/NEJMoa1803917

    Article  CAS  PubMed  Google Scholar 

  33. Goldberg AC, Leiter LA, Stroes ESG et al (2019) 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 322:1780–1788. https://doi.org/10.1001/jama.2019.16585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Laufs U, Banach M, Mancini GBJ et al (2019) Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J Am Heart Assoc 8:e11662. https://doi.org/10.1161/JAHA.118.011662

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ballantyne CM, Banach M, Mancini GBJ et al (2018) Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study. Atherosclerosis 277:195–203. https://doi.org/10.1016/j.atherosclerosis.2018.06.002

    Article  CAS  PubMed  Google Scholar 

  36. Ballantyne CM, Laufs U, Ray KK et al (2020) Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol 27:593–603. https://doi.org/10.1177/2047487319864671

    Article  PubMed  Google Scholar 

  37. Ray KK, Reeskamp LF, Laufs U et al (2021) Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J. https://doi.org/10.1093/eurheartj/ehab718

    Article  PubMed  PubMed Central  Google Scholar 

  38. Banach M, Duell PB, Gotto AMJ et al (2020) Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia. JAMA Cardiol 5:1124–1135. https://doi.org/10.1001/jamacardio.2020.2314

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Deutschland

    Andrea Baessler &  Marcus Fischer

  2. Klinik für Kardiologie, Angiologie, Pneumologie und Intensivmedizin, Goldberg-Klinik Kelheim, Kelheim, Deutschland

    Marcus Fischer

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  1. Andrea Baessler
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Correspondence to Andrea Baessler.

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Die Autoren machen folgende Angaben zu Honoraren für Vorträge oder Beratung: A. Baessler: Amgen, Sanofi, Novartis, Daiichi Sankyo, Amarin, Pfizer. M. Fischer: Amgen, Sanofi, Daiichi Sankyo, Amarin, Bayer.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Baessler, A., Fischer, M. Neue Optionen zur Intensivierung der lipidsenkenden Therapie. Herz 47, 212–219 (2022). https://doi.org/10.1007/s00059-022-05111-z

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