Literature Review: Efektivitas dan Efek Samping PCSK9 Inhibitor (Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor) dengan Golongan Statin pada Pasien Penderita Kolesterol
Keywords:
Alirocumab’ Bococizumab, Evolocumab, Cholesterol, Statins
Abstract
Cholesterol is an essential molecule in the human body, but excessive levels can lead to various diseases, including hypercholesterolemia. The management of high cholesterol involves the use of statins and PCSK9 inhibitors. This study aims to compare the effectiveness and side effects of these two drug classes.This study is a literature review conducted from August to September using articles from the PubMed database with keywords related to PCSK9 inhibitors and statins. The data were analyzed through bibliometric analysis using VOSviewer software with keywords such as PCSK9 inhibitor, alirocumab, bococizumab, and evolocumab.The results showed that PCSK9 inhibitors could reduce LDL-C levels by 57-61% with a good safety profile, although side effects such as injection site reactions were observed. In comparison, statins reduced LDL-C levels by 18-55% and increased HDL-C levels by up to 15%, but their side effects included muscle disorders and liver function impairment. PCSK9 inhibitors provide an additional solution for patients who do not respond optimally to statins. Conclusion: PCSK9 inhibitors are effective in lowering LDL-C in patients who have difficulty achieving target levels with statin therapy alone.
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Roth, Eli., John, J. P., Kastelein., Christopher, P., et al. (2020). Journal of Clinical Lipidology. 2020;14:707–719.
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Teramoto, T., Akira, K., Ahirio, K., et al. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids in Health and Disease. 2017;16(121):1-8.
Ballantyne, C. M. Joel, N., Anne. C., William, D., et al., (2015). Results of Bococizumab, A Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, from a Randomized, Placebo-Controlled, Dose-Ranging Study in Statin-Treated Subjects With Hypercholesterolemia. Am J Cardiol. 2015;115:1212e1221.
Fazio, S., David, G. R., Tengshang, J., Hong, W., et al. Effects of 12 weeks of treatment with intravenously administered bococizumab, a humanized monoclonal antibody blocking proprotein convertase subtilisin/kexin type 9, in hypercholesterolemic subjects on high-dose statin. Wiley Cardiovascular Therapeutics. 2017. DOI: 10.1111/1755-5922.12308.
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Yokote, K., Shigeto, K., et al. Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naïve. Circulation Journal. 2017;81.
Ridker, P. M., Lynda, M. R., John, J. P. K. Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab. Journal of clinical Lipidology. 2018;12(4):P958-965.
Hirayama, A., Narimon, H., Masayuki, Y., Shizuya, Y., Fannie, H., Scott, M., Wassserman., Tamio, T. Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk. Circulation Journal. 2014;78:1073-1082.
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Emily, M., Buchulz, M. D., et al. Prevalence and Predictors of Cholesterol Screening, Awareness, and Statin Treatment Among US Adults With Familial Hypercholesterolemia or Other Forms of Severe Dyslipidemia (1999–2014). American Heart Assosiation. Circulation. 2018;137(21):2218-2230.
WHO. Word Health Organization, International Society Of Hypertension Writing. World Health Organization. 2019.
Kementerian Kesehatan Republik Indonesia. Profil Penyakit Tidak Menular Tahun 2018. Kemenkes RI Tahun 2017.
Kemenkes RI. Riset Kesehatan Dasar (Riskesdas). Kemenkes : Jakarta. 2018.
Dewi, I. P., Maria. (2017). Editorial Peranan Obat Golongan Statin. Berkala Ilmiah Kedokteran Duta Wacana; Vol 2(3).
Paulina, A., Martianus, P. A., Rizky, H. Evaluasi Penggunaaan Obat Kolesterol Pada Pasien Hiperlipiemia Di Instalasi Rawat Jalan Rumah Sakit Mutiara Bunda. Jurnal Instalasi Farmasi. 2023; 6(1).
Udin, B. & Eva. K. Literature Review: Mekanisme Kerja Obat Antidislipidemia. Jurnal Ilmiah Bakti Farmasi. 2021; 6(1).
Al Husaeni, D. F., and Al Husaeni, D. N. Computational bibliometric analysis of research on science and Islam with VOSviewer: Scopus database in 2012 to 2022. ASEAN Journal of Religion, Education, and Society. 2022;1(1):39-48.
Santos, R., Albert, W., Sonia, C., et al. Alirocumab in Pediatric Patients With Heterozygous Familial Hypercholesterolemia A Randomized Clinical Trial. JAMA Pediatric. 2024;178(3):283-293. doi:10.1001/jamapediatrics.2023.6477.
Sabatine, Marc. S., Robert, P., et al. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events. The new england journal of medicine. 2015;372(6):1500-1509.
Blom, D. J., Hala, T., Bolognese, M., et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370:1809-19.
Sabatine, Marc. S., Robert, P., et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. The new england journal of medicine. 2017;376(18):1713-1722.
Al Husaeni, D. F., and Al Husaeni, D. N. Computational bibliometric analysis of research on science and Islam with VOSviewer: Scopus database in 2012 to 2022. ASEAN Journal of Religion, Education, and Society. 2022;1(1):39-48.
Sudarjat, H. Computing Bibliometric Analysis with Mapping Visualization using VOSviewer on “Pharmacy” and “Special Needs” Research Data in 2017-2021. ASEAN Journal of Community and Special Needs Education. 2023;2(1), 1–8.
Al Husaeni, D. F., Wi, N. A., Asep, B. D. N., Mauhibur, R., et al. How Technology Can Change Educational Research? Definition, Factors for Improving Quality of Education and Computational Bibliometric Analysis. ASEAN Journal of Science and Engineering. 2024;4(2):127-166.
Karim, A., Joko, S., Rahma, P. N., Ana, L. U. Analisis Bibliometrik Menggunakan Vosviewer Terhadap Trend Riset Matematika Terapan Di Google Scholar. Jurnal Riset Pendidikan Matematika Jakarta. 2021;3(2):23-33.
Nurfauzan & Hanani. Analisis Bibliometrik Trend Penelitian Covid-19 di Indonesia pada Bidang Bisnis dan Manajemen. Jurnal Bisnis STRATEGI. 2021;30(2):90 – 100.
Prameswari, D. C. Konsumsi Pisang Dalam Menurunkan Kadar Kolesterol Darah. Jurnal Penelitian Perawat Profesional. 2021;3(3).
Purnama, D. I., & Maria, S. M. Editorial; Peranan Obat Golongan Statin. Cardiovascular Drugs and Therapy. 2017; 22(4):321–338.
Ferri, N., & Corsini, A. Clinical Pharmacology of Statins: an Update. Current Atherosclerosis Reports. 2020;22(7). https://doi.org/10.1007/s11883-020- 00844-w.
McTaggart, F., Jones, P. Effects of Statins on High-Density Lipoproteins: A Potential Contribution to Cardiovascular Benefit. Cardiovascular Drugs and Therapy. 2008;22(4):321-338. doi:10.1007/s10557-008-6113-z.
Basiak, M., Kosowski, M., Cyrnek, M., & Bułdak, Ł. Pleiotropic Effects of PCSK-9 Inhibitors. International Journal of Molecular Science. 2021;22:3144.
Chen, H., Qi, X., Faulkner, R. A., Schumacher, M. M., Donnelly, L. M., DeBose-Boyd, R. A., & Li, X. Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain. Nature Communications. 2022;13(1):1–12. https://doi.org/10.1038/s41467-022- 32025-5.
Roth, Eli., John, J. P., Kastelein., Christopher, P., et al. (2020). Journal of Clinical Lipidology. 2020;14:707–719.
Robinson, J. G., Michel, F., Michel, K., et al. Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events. The new england journal of medicine. 2015;372(16):1489-1499.
Teramoto, T., Akira, K., Ahirio, K., et al. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids in Health and Disease. 2017;16(121):1-8.
Ballantyne, C. M. Joel, N., Anne. C., William, D., et al., (2015). Results of Bococizumab, A Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, from a Randomized, Placebo-Controlled, Dose-Ranging Study in Statin-Treated Subjects With Hypercholesterolemia. Am J Cardiol. 2015;115:1212e1221.
Fazio, S., David, G. R., Tengshang, J., Hong, W., et al. Effects of 12 weeks of treatment with intravenously administered bococizumab, a humanized monoclonal antibody blocking proprotein convertase subtilisin/kexin type 9, in hypercholesterolemic subjects on high-dose statin. Wiley Cardiovascular Therapeutics. 2017. DOI: 10.1111/1755-5922.12308.
Yokote. K., Akiyuki, S., Yinhua, L., et al. (2019). Pharmacokinetics and exploratory efficacy biomarkers of bococizumab, an anti-PCSK9 monoclonal antibody, in hypercholesterolemic Japanese subjects. International Journal of Clinical Pharmacology and Therapeutics. 2019;57(12):575-589.
Yokote, K., Shigeto, K., et al. Efficacy and Safety of Bococizumab (RN316/PF-04950615), a Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, in Hypercholesterolemic Japanese Subjects Receiving a Stable Dose of Atorvastatin or Treatment-Naïve. Circulation Journal. 2017;81.
Ridker, P. M., Lynda, M. R., John, J. P. K. Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: Results from the SPIRE randomized trials of bococizumab. Journal of clinical Lipidology. 2018;12(4):P958-965.
Hirayama, A., Narimon, H., Masayuki, Y., Shizuya, Y., Fannie, H., Scott, M., Wassserman., Tamio, T. Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk. Circulation Journal. 2014;78:1073-1082.
Pfizer. Pfizer discontinues global development of bococizumab, its investigational PCSK9 inhibitor. http://www.pfizer.com/news/ press-release/press-release-detail/pfizer_discontinues_global_development_of_bococizumab_its_investigational_pcsk9_inhibitor. Accessed July 11, 2017.
Published
2025-06-30
How to Cite
Affandhy, A., Sudarjat, H., Hilmi, I., Shadrina, J., & Dzannuba, F. L. D. (2025). Literature Review: Efektivitas dan Efek Samping PCSK9 Inhibitor (Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor) dengan Golongan Statin pada Pasien Penderita Kolesterol. Jurnal Sehat Mandiri, 20(1), 66-79. https://doi.org/https://doi.org/10.33761/jsm.v20i1.1746
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