Hyperlipidämie: Welche Rolle spielen PCSK9-Inhibitoren?

Was ist neu?

Risikostratifizierung Die zielwertgerechte Senkung des LDL-Cholesterins (LDL-C) ist eine effektive Maßnahme zur kardiovaskulären Prävention. Derzeit erreicht ein Großteil der Patienten in Deutschland ihren individuellen LDL-C-Zielwert nicht.

Therapie Durch konsequente Anwendung von Statinen in Kombination mit Ezetimib lässt sich bei vielen Patienten der entsprechende LDL-C-Zielwert erreichen. Inhibitoren der Proproteinkonvertase Subtilisin/Kexin Typ 9 (PCSK9) sind eine neue, nebenwirkungsarme Möglichkeit der intensiven LDL-C-Senkung. Zwei große Endpunktstudien konnten die Wirksamkeit und Sicherheit bereits belegen. Bei ausgewählten kardiovaskulären Höchstrisikopatienten ermöglicht der Einsatz von PCSK9-Inhibitoren eine sichere und effektive LDL-C-Senkung.

Abstract

PCSK9 inhibitors are a new and safe option of lowering LDL cholesterol. This article summarizes current recommendations for the use of PCSK9 inhibitors. Statins and ezetimibe are still the basis of cholesterol-lowering therapy. Through their use, the largest proportion of patients can be adequately treated. PCSK9 inhibitors should be used in patients at very high cardiovascular risk if, despite the maximum tolerated statin/ezetimibe therapy, an LDL-C reduction of more than 50 % would be needed to achieve the recommended LDL-C target. The use in patients with familial hypercholesterolemia is usually carried out according to this scheme as well. For statin intolerance, PCSK9 inhibitors should be considered in patients at very high cardiovascular risk who have not tolerated low doses of at least two different statins/ezetimibe.

Schlüsselwörter

LDL-Cholesterin - PCSK9-Antikörper - Prävention - Dyslipidämie

Key words

LDL cholesterol - PCSK9 antibodies - prevention - dyslipidemia

• Literatur

• 1 Catapano AL, Graham I, De Backer G. et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37: 2999-3058
• 2 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
• 3 Giugliano RP, Pedersen TR, Park JG. et al. 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 2017; 390: 1962-1971
• 4 Baigent C, Blackwell L, Emberson J. et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet 2010; 376: 1670-1681
• 5 Bohula EA, Morrow DA, Giugliano RP. et al. Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention. J Am Coll Cardiol 2017; 69: 911-921
• 6 Marz W, Dippel FW, Theobald K. et al. Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients at high and very-high cardiovascular risk: Real-world evidence from Germany. Atherosclerosis 2018; 268: 99-107
• 7 Sabatine MS, Giugliano RP, Keech AC. et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017; 377: 787-788
• 8 McCullough PA, Ballantyne CM, Sanganalmath SK. et al. Efficacy and Safety of Alirocumab in High-Risk Patients With Clinical Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial Hypercholesterolemia (from 5 Placebo-Controlled ODYSSEY Trials). Am J Cardiol 2018; 121: 940-948
• 9 Gemeinsamer Bundesausschuss. Richtlinie über die Verordnung von Arzneimitteln in der vertragsärztlichen Versorgung. Anlage III. Im Internet: https://www.g-ba.de/downloads/83-691-466/AM-RL-III-Verordnungseinschraenkung_2017-11-04.pdf ; Stand: 20.8.2018
• 10 Landmesser U, Chapman MJ, Farnier M. et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur Heart J 2017; 38: 2245-2255
• 11 Moriarty PM, Parhofer KG, Babirak SP. et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J 2016; 37: 3588-3595
• 12 Giugliano RP, Mach F, Zavitz K. et al. Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med 2017; 377: 633-643
• 13 Steg P. on behalf of the ODYSSEY OUTCOMES Investigators and Committees. The ODYSSEY OUTCOMES Trial: Topline Results Alirocumab in Patients After Acute Coronary Syndrome. Oral presentation. American College of Cardiology – 67th Scientific Sessions; March 10, 2018