Hypercholesterinämie und kardiovaskuläres Risiko

Für die Prävention kardiovaskulärer Ereignisse stellt die Reduktion des LDL-Cholesterins (LDL-C) eine entscheidende Maßnahme dar. Zwar bleiben Statine das Mittel der ersten Wahl, jedoch stehen mit Ezetimib, Bempedoinsäure und der PCSK9-Inhibition weitere LDL-C-senkende Wirkstoffe zur Verfügung. Diese sollten zur LDL-C-Zielwerterreichung und somit zur kardiovaskulären Risikoreduktion insbesondere bei Hochrisikopatienten frühzeitig zum Einsatz kommen.

Abstract

Pharmacological reduction of LDL-cholesterol (LDL-C) is a major treatment strategy in limiting atherosclerotic cardiovascular (ASCVD) risk. Statins remain the primary therapeutic cornerstone in ASCVD prevention. Furthermore, ezetimibe, bempedoic acid, and PCSK9 inhibition have recently also shown to reduce cardiovascular risk. Unfortunately, a treatment gap remains between guideline-recommended LDL-C goals and what is achieved in real-world practice. An important reason for this is the limited use of novel and effective non-statin lipid-lowering therapies. In order to achieve LDL-C treatment goals and, ultimately, reduction of cardiovascular events, a combination lipid-lowering therapy needs to be considered as the standard of care for patients at very high cardiovascular risk.

Schlüsselwörter

Hypercholesterinämie - kardiovaskulär - Risiko - LDL-Cholesterin

Keywords

hypercholesterolemia - cardiovascular - risk - LDL-cholesterol

Publication History

Article published online:
04 August 2023

• Literatur

• 1 Ford ES, Ajani UA, Croft JB. et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med 2007; 356: 2388-2398
• 2 Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396: 1204-1222
• 3 Toppila I, Ukkola-Vuoti L, Perttila J. et al. Cardiovascular event rate and death in high-risk secondary prevention patient cohort in Finland: A registry study. Clin Cardiol 2022; 45: 342-351
• 4 Yusuf S, Hawken S, Ounpuu S. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-952
• 5 Scheidt-Nave C, Du Y, Knopf H. et al. Prevalence of dyslipidemia among adults in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS 1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2013; 56: 661-667
• 6 Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986; 256: 2823-2828
• 7 Lui DTW, Lee ACH, Tan KCB. Management of Familial Hypercholesterolemia: Current Status and Future Perspectives. J Endocr Soc 2021; 5: bvaa122
• 8 Baigent C, Keech A, Kearney PM. et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278
• 9 Nicholls SJ, Kataoka Y, Nissen SE. et al. Effect of Evolocumab on Coronary Plaque Phenotype and Burden in Statin-Treated Patients Following Myocardial Infarction. JACC Cardiovasc Imaging 2022; 15: 1308-1321
• 10 Raber L, Ueki Y, Otsuka T. et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA 2022; 327: 1771-1781
• 11 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
• 12 Boekholdt SM, Hovingh GK, Mora S. et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol 2014; 64: 485-494
• 13 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
• 14 Gouni-Berthold I, Schaper F, Schatz U. et al. Low-density lipoprotein cholesterol goal attainment in Germany: Results from the DA VINCI study. Atheroscler Plus 2022; 50: 10-16
• 15 Sturzebecher PE, Tunnemann-Tarr A, Tuppatsch K. et al. Treatment and LDL cholesterol adjustment in patients with high and very high cardiovascular risk in Germany compared with Europe – data from the SANTORINI registry. Dtsch Med Wochenschr 2023; 148 (09) 55-64
• 16 Cholesterol Treatment Trialists C, Baigent C, Blackwell L. et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376: 1670-1681
• 17 Jones PH, Nair R, Thakker KM. Prevalence of dyslipidemia and lipid goal attainment in statin-treated subjects from 3 data sources: a retrospective analysis. J Am Heart Assoc 2012; 1: e001800
• 18 LaRosa JC, Grundy SM, Waters DD. et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425-1435
• 19 Parker BA, Capizzi JA, Grimaldi AS. et al. Effect of statins on skeletal muscle function. Circulation 2013; 127: 96-103
• 20 Zhang H, Plutzky J, Skentzos S. et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med 2013; 158: 526-534
• 21 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
• 22 Nissen SE, Lincoff AM, Brennan D. et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N Engl J Med 2023; 388 (15) 1353-1364
• 23 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
• 24 Schwartz GG, Steg PG, Szarek M. et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med 2018; 379: 2097-2107
• 25 Sudhop T, Lutjohann D, Kodal A. et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002; 106: 1943-1948
• 26 Makhmudova U, Samadifar B, Maloku A. et al. Intensive lipid-lowering therapy for early achievement of guideline-recommended LDL-cholesterol levels in patients with ST-elevation myocardial infarction (“Jena auf Ziel”). Clin Res Cardiol 2023;
• 27 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
• 28 Pinkosky SL, Newton RS, Day EA. et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun 2016; 7: 13457
• 29 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, placebo-controlled study. Atherosclerosis 2018; 277: 195-203
• 30 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
• 31 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
• 32 Laufs U, Banach M, Mancini GBJ. et al. Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance. J Am Heart Assoc 2019; 8: e011662
• 33 Ray KK, Bays HE, Catapano AL. et al. Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol. N Engl J Med 2019; 380: 1022-1032
• 34 Gemeinsamer Bundesausschuss. Beschluss des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage III: Nummer 35a, Nummer 35b und Nummer 35c – Bempedoinsäure. Berlin: Gemeinsamer Bundesausschuss; 2023
• 35 Seidah NG, Awan Z, Chretien M. et al. PCSK9: a key modulator of cardiovascular health. Circ Res 2014; 114: 1022-1036
• 36 Ballantyne CM, Banka P, Mendez G. et al. Efficacy and safety of the oral PCSK9 inhibitor MK-0616: a phase 2b randomized controlled trial. J Am Coll Cardiol 2023; 81 (16) 1553-1564
• 37 Koren MJ, Lundqvist P, Bolognese M. et al. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 2014; 63: 2531-2540
• 38 Robinson JG, Nedergaard BS, Rogers WJ. et al. Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial. JAMA 2014; 311: 1870-1882
• 39 Nair JK, Willoughby JL, Chan A. et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc 2014; 136: 16958-16961
• 40 Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S. et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet 2014; 383: 60-68
• 41 Ray KK, Wright RS, Kallend D. et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med 2020; 382: 1507-1519
• 42 Raal FJ, Kallend D, Ray KK. et al. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med 2020; 382: 1520-1530