The therapeutic effect of PCSK9 inhibitors on dyslipidemia: one-year follow up

Submitted: 18 August 2024
Accepted: 2 September 2024
Published: 13 September 2024
Abstract Views: 158
PDF: 107
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Despite the availability of statins and lifestyle modifications, many patients with Dyslipidemia struggle to achieve optimal low-density lipoprotein cholesterol (LDL-C) control. PCSK9 inhibitors offer a promising new therapeutic option with superior LDL-C lowering efficacy compared to statins. However, data on their real-world use, particularly in Iran, is limited. This study aims to address this gap by investigating the one-year effects of evolocumab on lipid profiles and potential cardiovascular outcomes in Iranian patients with Familial Hypercholesterolemia (FH).This single-center, prospective study evaluated evolocumab effectiveness in lowering LDL-C in 50 Iranian adults with FH. Participants with a documented LDL-C > 190 mg/dL on existing cholesterol medications (excluding PCSK9 inhibitors) and a clinical FH diagnosis was included. After baseline assessments (medical history, demographics, lipid profile), evolocumab was administered subcutaneously every two weeks for one year. Follow-up assessments at year one measured changes in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. The study enrolled 50 participants with an average age of 55 years old (range 35-80 years).Treatment with evolocumab led to significant improvements in lipid profiles at all follow-up points compared to baseline. On average, LDL-C levels decreased by 105.24 mg/dL, triglycerides decreased by 59.20 mg/dL, and HDL-C levels increased by a modest but significant 4.5 mg/dL after one year(p<0.001). Subgroup analysis revealed no statistically significant interactions between baseline demographics (age, sex, BMI) or lifestyle habits (smoking, alcohol) and changes in lipid levels(p>0.05). However, a significant interaction emerged between baseline lipid levels and their corresponding reductions, suggesting greater improvement in patients with higher baseline values(p<0.05). It is noteworthy that no new cardiovascular events were reported during the study period. This study demonstrates the effectiveness of evolocumab in improving lipid profiles in Iranian patients with FH. The observed reductions in LDL-C and triglycerides, along with a modest increase in HDL-C, suggest potential benefits for cardiovascular risk reduction. The absence of new cardiovascular events during the study is encouraging, but further research with larger and longer-term follow-up is needed to confirm these findings and assess the long-term safety and impact on quality of life.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Plaudit

Hovingh GK, Raal FJ, Dent R, et al. Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol 2017;11:1448-57. DOI: https://doi.org/10.1016/j.jacl.2017.09.003
Luquero A, Badimon L, Borrell-Pages M. PCSK9 functions in atherosclerosis are not limited to plasmatic LDL-cholesterol regulation. Front Cardiovasc Med 2021;8:639727. DOI: https://doi.org/10.3389/fcvm.2021.639727
Azimi M, Ahmadi E, Aghaie F, et al. The Effect of Alcoholic Extract of Thymus Vulgaris on Hepatic Enzymes Activity and Apoptosis-Related Gene Expression in Streptozotocin-Induced Diabetic Rats. Evid Based Complement Alternat Med 2022;2022:2948966. DOI: https://doi.org/10.1155/2022/2948966
Vaezi Z, Amini A. Familial hypercholesterolemia. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556009/
Jalili C, Darakhshan S, Azimi M. Harmine mitigates liver injury induced by mercuric chloride via the inhibition of oxidative stress. Res J Pharmacogn 2021;8:13-23.
Rezaei M, Rahmani E, Khouzani SJ, et al. Role of artificial intelligence in the diagnosis and treatment of diseases. Kindle 2023;3:1-60.
Albuquerque J, Alves AC, Medeiros AM, et al. Classification methods applied to familial hypercholesterolemia diagnosis at pediatric age: Comparison of Simon Broome criteria with modified decision tree models. Atherosclerosis 2020;315:e205. DOI: https://doi.org/10.1016/j.atherosclerosis.2020.10.642
Safari H, Ajudani R, Savaie M, et al. Intracerebral hemorrhage in methanol toxicity patients during COVID-19 pandemic: case report and review of literature. Forensic Toxicol 2024:1-6. DOI: https://doi.org/10.1007/s11419-023-00680-y
Kasichayanula S, Grover A, Emery MG, et al. Clinical pharmacokinetics and pharmacodynamics of evolocumab, a PCSK9 inhibitor. Clin Pharmacokin 2018;57:769-79. DOI: https://doi.org/10.1007/s40262-017-0620-7
Wei CC, Razzak AA, Ghasemi H, et al. Ca2+ binding shifts dimeric dual oxidase's truncated EF-hand domain to monomer. Biophys Chem 2024:107271. DOI: https://doi.org/10.1016/j.bpc.2024.107271
Liu C, Chen J, Chen H, et al. PCSK9 inhibition: from current advances to evolving future. Cells 2022;11:2972. DOI: https://doi.org/10.3390/cells11192972
Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 2015;36:2996-3003. DOI: https://doi.org/10.1093/eurheartj/ehv370
Raal FJ, Stein EA, Dufour R. PCSK9 Inhibition with evolocumab (amg 145) in heterozygous familial hypercholesterolemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. J Vascular Surg 2015;62:1368. DOI: https://doi.org/10.1016/j.jvs.2015.09.006
Blom DJ, Harada-Shiba M, Rubba P, et al. Efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia: the ODYSSEY HoFH trial. J Am Coll Cardiol 2020;76:131-42. DOI: https://doi.org/10.1016/j.jacc.2020.05.027
Toth PP, Bray S, Villa G, et al. Network meta‐analysis of randomized trials evaluating the comparative efficacy of lipid‐lowering therapies added to maximally tolerated statins for the reduction of low‐density lipoprotein cholesterol. J Am Heart Assoc 2022;11:e025551. DOI: https://doi.org/10.1161/JAHA.122.025551
Rosenson RS, Jacobson TA, Preiss D, et al. Efficacy and safety of the PCSK9 inhibitor evolocumab in patients with mixed hyperlipidemia. Cardiovasc Drugs Ther 2016;30:305-13. DOI: https://doi.org/10.1007/s10557-016-6666-1
Zhang Y, Suo Y, Yang L, et al. Effect of PCSK9 inhibitor on blood lipid levels in patients with high and very‐high CVD risk: a systematic review and meta‐analysis. Cardiol Res Pract 2022;2022:8729003. DOI: https://doi.org/10.1155/2022/8729003
Sabatine MS. PCSK9 inhibitors: clinical evidence and implementation. Nature Rev Cardiol 2019;16:155-65. DOI: https://doi.org/10.1038/s41569-018-0107-8
Paquette M, Faubert S, Saint-Pierre N, et al. Sex differences in LDL-C response to PCSK9 inhibitors: A real world experience. J Clini Lipidol 2023;17:142-9. DOI: https://doi.org/10.1016/j.jacl.2022.12.002
Hess CN, Low Wang CC, Hiatt WR. PCSK9 inhibitors: mechanisms of action, metabolic effects, and clinical outcomes. Ann Rev Med 2018;69:133-45. DOI: https://doi.org/10.1146/annurev-med-042716-091351
Mohamed F, Mansfield B, Raal FJ. Targeting PCSK9 and Beyond for the management of low-density lipoprotein cholesterol. J Clin Med 2023;12:5082. DOI: https://doi.org/10.3390/jcm12155082
Ginsberg HN, Rader DJ, Raal FJ, et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia and LDL-C of 160 mg/dl or higher. Cardiovasc Drugs Ther 2016;30:473-83. DOI: https://doi.org/10.1007/s10557-016-6685-y
Iqbal F, Baker WS, Khan MI, et al. Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism. Br J Pharmacol 2017;174:3986-4006. DOI: https://doi.org/10.1111/bph.13743
Ma W, Guo X, Ma Y, Hu Z. Meta-analysis of randomized clinical trials comparing PCSK9 monoclonal antibody versus ezetimibe/placebo in patients at high cardiovascular risk. Atherosclerosis 2021;326:25-34. DOI: https://doi.org/10.1016/j.atherosclerosis.2021.04.008
Berman AN, Blankstein R. Optimizing dyslipidemia management for the prevention of cardiovascular disease: a focus on risk assessment and therapeutic options. Curr Cardiol Rep 2019;21:1-0. DOI: https://doi.org/10.1007/s11886-019-1175-z
Karantas ID, Okur ME, Okur NÜ, Siafaka PI. Dyslipidemia management in 2020: an update on diagnosis and therapeutic perspectives. Endocr Metabol Immune Disorders-Drug Targets 2021;21:815-34. DOI: https://doi.org/10.2174/1871530320666200810144004
Lorenzatti AJ, Eliaschewitz FG, Chen Y, et al. Rationale and design of a randomized study to assess the efficacy and safety of evolocumab in patients with diabetes and dyslipidemia: the BERSON clinical trial. Clin Cardiol 2018;41:1117-22. DOI: https://doi.org/10.1002/clc.23018
AlHajri L, AlHadhrami A, AlMheiri S, et al. The efficacy of evolocumab in the management of hyperlipidemia: a systematic review. Ther Adv Cardiovasc Dis 2017;11:155-69. DOI: https://doi.org/10.1177/1753944717698925
Lazarte J, Hegele RA. Dyslipidemia management in adults with diabetes. Can J Diabetes 2020;44:53-60. DOI: https://doi.org/10.1016/j.jcjd.2019.07.003
Muscoli S, Ifrim M, Russo M, et al. Current options and future perspectives in the treatment of dyslipidemia. J Clin Med 2022;11:4716. DOI: https://doi.org/10.3390/jcm11164716

How to Cite

Moshkani Farahani, M., Nasiri, A., Salari, M., & Shamsedini, A. (2024). The therapeutic effect of PCSK9 inhibitors on dyslipidemia: one-year follow up. European Journal of Translational Myology, 34(3). https://doi.org/10.4081/ejtm.2024.12937