Therapieoptionen zur LDL-C-Senkung zusätzlich zu Statinen

ZUSAMMENFASSUNG

Die aktuellen Leitlinien für Dyslipidämie heben Statine als Eckpfeiler der pharmakologischen Lipidsenkungstherapie hervor. Ezetimib, PCSK9-Antikörper sowie Bempedosäure und Inclisiran sind neu verfügbare Optionen zur weiteren Senkung des LDL-C. Da die moderne Lipidsenkungstherapie durch einen individuellen „Treat-to-Target“-Ansatz gekennzeichnet ist, soll dieser Beitrag zu einem besseren Verständnis des Cholesterinstoffwechsels beitragen, um den rationalen Einsatz früher individualisierter Kombinationstherapien zu unterstützen.

Publication History

Article published online:
09 December 2022

• Literatur

• 1 Müller-Wieland D, Merkel M, Verket M. et al [Pathophysiological principles of dyslipoproteinaemia]. Dtsch Med Wochenschr 2021; 146: e103-e111
• 2 Mach F, Baigent C, Catapano AL. et al 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-188
• 3 Weingärtner O, Landmesser U, März W. et al Kommentar zu den Leitlinien (2019) der ESC/EAS zur Diagnostik und Therapie der Dyslipidämien. Kardiologe 2020; 14: 256-266
• 4 Laufs U, Weingärtner O, Kassner U. et al [State of the Art: Statin Therapy]. Dtsch Med Wochenschr 2022; 147: 62-68
• 5 Cannon CP, Blazing MA, Giugliano RP. et al Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372: 2387-2397
• 6 Sabatine MS, Giugliano RP, Keech AC. et al Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 376: 1713-1722
• 7 Schwartz GG, Steg PG, Szarek M. et al Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379: 2097-2107
• 8 Visseren FLJ, Mach F, Smulders YMet al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42: 3227-3337
• 9 Helgadottir A, Thorleifsson G, Alexandersson KF. et al Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease. Eur Heart J 2020; 41: 2618-2628
• 10 Weingärtner O, Patel SB, Lütjohann D. Itʼs time to personalize and optimize lipid-lowering therapy. Eur Heart J 2020; 41: 2629-2631
• 11 Lütjohann D, Stellaard F, Mulder MT. et al The emerging concept of „individualized cholesterol-lowering therapy“: A change in paradigm. Pharmacol Ther 2019; 199: 111-116
• 12 Karlson BW, Wiklund O, Palmer MK. et al Variability of lowdensity lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER. Eur Heart J Cardiovasc Pharmacother 2016; 02: 212-217
• 13 Altmann SW, Davis Jr HR, Zhu LJ. et al Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004; 303: 1201-1204
• 14 Sudhop T, Lütjohann D, Kodal A. et al Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002; 106: 1943-1948
• 15 Weingärtner O, Lütjohann D, Böhm M. et al [Cholesterol homeostasis and cardiovascular risk]. Dtsch Med Wochenschr 2011; 136: 34-38
• 16 Bohula EA, Morrow DA, Giugliano RP. et al Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention. J Am Coll Cardiol 2017; 69: 911-921
• 17 Eisen A, Cannon CP, Blazing MA. et al The benefit of adding ezetimibe to statin therapy in patients with prior coronary artery bypass graft surgery and acute coronary syndrome in the IMPROVE-IT trial. Eur Heart J 2016; 37: 3576-3584
• 18 Bohula EA, Wiviott SD, Giugliano RP. et al Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial). Circulation 2017; 136: 2440-2450
• 19 Bach RG, Cannon CP, Giugliano RP. et al Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol 2019; 04: 846-854
• 20 Makhmudova U, Schulze PC, Davis HR. et al Lipid lowering in patients 75 years and older. World J Cardiol 2021; 13: 526-532
• 21 Ouchi Y, Sasaki J, Arai H. et al Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial. Circulation 2019; 140: 992-1003
• 22 Katzmann JL, Sorio-Vilela F, Dornstauder E. et al 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 2022; 111: 243-252
• 23 Goldberg AC, Leiter LA, Stroes ESG. et al 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 2019; 322: 1780-1788
• 24 Bilen O, Ballantyne CM. Bempedoic Acid (ETC-1002): an Investigational Inhibitor of ATP Citrate Lyase. Curr Atheroscler Rep 2016; 18: 61
• 25 Ballantyne CM, Banach M, Mancini GBJ. et al Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebocontrolled study. Atherosclerosis 2018; 277: 195-203
• 26 Ballantyne CM, Laufs U, Ray KK. et al 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 2020; 27: 593-603
• 27 Laufs U, Parhofer KG, Ginsberg HN. et al Clinical review on triglycerides. Eur Heart J 2020; 41: 99-109c
• 28 Laina A, Gatsiou A, Georgiopoulos G. et al RNA Therapeutics in Cardiovascular Precision Medicine. Front Physiol 2018; 09: 953
• 29 Ray KK, Landmesser U, Leiter LA. et al Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. N Engl J Med 2017; 376: 1430-1440
• 30 Schettler V, Wieland E. [Effects of LDL-apheresis–more than reduction of cholesterol?]. Dtsch Med Wochenschr 2007; 132: 575-578
• 31 Thompson GR. LDL apheresis. Atherosclerosis 2003; 167: 1-13
• 32 Jaeger BR, Richter Y, Nagel D. et al Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events. Nat Clin Pract Cardiovasc Med 2009; 06: 229-239
• 33 Ray KK, Molemans B, Schoonen WM. et al EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study. Eur J Prev Cardiol 2021; 28: 1279-1289
• 34 Allahyari A, Jernberg T, Hagström E. et al Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study. Eur Heart J 2020; 41: 3900-3909
• 35 Ray KK, Reeskamp LF, Laufs U. et al Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J 2022; 43: 830-833