Turn in hypercholesterolemia treatment – PCSK9 inhibitors. What we know about the alirocumab (product Praluent®) yet?
Authors:
Richard Češka 1; Lucie Votavová 2; Tanja Aleksičová 2
Authors‘ workplace:
Centrum preventivní kardiologie, III. interní klinika 1. LF UK a VFN v Praze, Česká republika
1; ScreenPro FH, z. s., Praha, Česká republika
2
Published in:
AtheroRev 2016; 1(1): 34-41
Category:
Reviews
Overview
At the present time there are novel hypolipidemics registered globally (alirocumab was the first drug of this group in the world registered by an American drug agency FDA) and in Europe, which in many ways differ from the medicines administered until now. They are bringing another advancement in the treatment of disorders of lipid metabolism and in preventive cardiology. Registered products are the alirocumab (product Praluent®) and the evolucumab (product Repatha®). Alirocumab is a fully human monoclonal antibody to PCSK-9 enzyme (proprotein convertase subtilisin kexin-9). PCSK-9 enzyme plays an important role in the metabolism of LDL-cholesterol through affecting the breakdown and eventually the amount and activity of LDL-receptors. From the clinical point of view it is essential that drugs from this group are administered parenterally, as a subcutaneous injection. In the case of Praluent® the interval between administration is two weeks. The dose is then 75 or 150 mg in a 1ml injection. From the clinical point of view it is particularly important that alirocumab decreases LDL-C concentrations by 50–60%, it decreases Lp/a/ levels by 25–30%, and it also positively influences other components of lipid metabolism and, above all, is very likely to have a potential to decrease a cardiovascular risk. Although the resuIts of morbidity and mortality studies are expected in the coming years, initial analyses strongly indicate a clinically significant reduction of CV events. Alirocumab, Praluent can be administered as monotherapy (mainly to statin-intolerant patients), however it will be primarily administered in combination with the other hypolipidemic drugs (in particular statins) where the effort to reach target values has not succeeded.
Key words:
alirocumab – familial hypercholesterolemia – hypercholesterolemia – hypolipidemics – Praluent®
Sources
1. Češka R et al. Familiární hypercholesterolemie. TRITON: Praha 2015. ISBN 978–80–7387–843–6.
2. Watts GF, Gidding S, Wierzbicki AS et al. Integrated Guidance on the Care of Familial Hypercholesterolaemia from the International FH Foundation. Int J Cardiol 2014; 171 (3): 309–325.
3. Reiner Z, Catapano AL, De BG et al. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32(14): 1769–1818.
4. Nordestgaard BG, Chapman MJ, Humphries SE et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society.Eur Heart J 2013; 34(45): 3478–3490.
5. Robinson JG, Farnier M, Krempf M. Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events. N Engl J Med 2015; 372(16): 1489–1499.
6. Moriarty PM, Jacobson TA, Bruckert E et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol 2014; 8(6): 554–561.
7. Lunven C, Paehler T, Poitiers F et al. A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects. Cardiovasc Ther 2014; 32(6): 297–301.
8. Kereiakes DJ, Robinson JG, Cannon CP et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J 2015; 169(6): 906–915.
9. Cannon CP, Cariou B, Blom D et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J 2015; 36(19): 1186–1194.
10. Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372(16): 1489–1499.
11. Bays H, Gaudet D, Weiss R et al. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab 2015; 100(8): 3140–3148.
12. Bays H, Farnier M, Gaudet D et al. Efficacy and safety of combining alirocumab with atorvastatin or rosuvastatin versus statin intensification or adding ezetimibe in high cardiovascular risk patients: ODYSSEY OPTIONS I and II [abstract]. Circulation 2015; 130(23): 2118–2119.
13. Roth E, Rader DJ, Moriarty P. Phase 3 randomized trial evaluating alirocumab every four weeks dosing as add-on to statin or as monotherapy: ODYSSEY CHOICE I [abstract no. 0254]. In: 17th International Symposium on Atherosclerosis. 2015.
14. Roth EM, Taskinen MR, Ginsberg HN et al. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized phase 3 trial. Int J Cardiol 2014; 176(1): 55–61.
15. Moriarty PM, Thompson PD, Cannon CP et al. ODYSSEY ALTERNATIVE: efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody, alirocumab, versus ezetimibe, in patients with statin intolerance as defined by a placebo run-in and statin rechallenge arm. Circulation 2014; 130(23): 2108–2109.
16. Kastelein JJ, Robinson JG, Farnier M. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolaemia not adequately controlled with current lipid-lowering therapy: results of ODYSSEY FH I and FH II studies [abstract no. 2125]. In: European Society of Cardiology 2015.
17. Ginsberg HN, Rader DJ, Raal FJ. ODYSSEY HIGH FH: efficacy and safety of alirocumab in patients with severe heterozygous familial hypercholesterolemia. Circulation 2014; 130(23): 2119.
18. Rosenson RS, Baker SK, JacobsonTA, Kopecky SL, Parker BA. An assessment by the statin muscle safety task force: 2014 update. J Clin Lipidol 2014; 8(3 Suppl): S58–S71.
19. Stroes ES, Thompson PD, Corsini A et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015; 36(17):1012–1022.
20. Bruckert E, Hayem G, Dejager S et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study. Cardiovasc Drugs Ther 2005; 19(6): 403–414.
21. Banach M, Rizzo M, Toth PP et al. Statin intolerance- an attempt at a unified definition. Position paper from an Internanational Lipid Expert Panel. Expert Opin Drug Saf 2015; 14(6): 935–955.
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Angiology Diabetology Internal medicine Cardiology General practitioner for adultsArticle was published in
Athero Review
2016 Issue 1
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