Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials

Qian, Geng; Li, Xuan; Sun, Qingjiao; Wang, Zhengzhong

doi:10.5603/cj.a2021.0110

Cited by 12 publications

(8 citation statements)

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“…The meta-analysis showed that PCSK9 inhibitors increased the expression of high-density lipoproteins (approximately 5.63–7.05%). However, the protective effect on lipoprotein A1 has not been confirmed through randomized controlled trials [ 44 ]. In addition, several large cohort studies have demonstrated the pheMR results of PCSK9 [ 39 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

Sun,

Yun,

Lin

et al. 2024

J Transl Med

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Background Ischemic heart disease is one of the leading causes of mortality worldwide, and thus calls for development of more effective therapeutic strategies. This study aimed to identify potential therapeutic targets for coronary heart disease (CHD) and myocardial infarction (MI) by investigating the causal relationship between plasma proteins and these conditions. Methods A two-sample Mendelian randomization (MR) study was performed to evaluate more than 1600 plasma proteins for their causal associations with CHD and MI. The MR findings were further confirmed through Bayesian colocalization, Summary-data-based Mendelian Randomization (SMR), and Transcriptome-Wide Association Studies (TWAS) analyses. Further analyses, including enrichment analysis, single-cell analysis, MR analysis of cardiovascular risk factors, phenome-wide Mendelian Randomization (Phe-MR), and protein-protein interaction (PPI) network construction were conducted to verify the roles of selected causal proteins. Results Thirteen proteins were causally associated with CHD, seven of which were also causal for MI. Among them, FES and PCSK9 were causal proteins for both diseases as determined by several analytical methods. PCSK9 was a risk factor of CHD (OR = 1.25, 95% CI: 1.13–1.38, P = 7.47E-06) and MI (OR = 1.36, 95% CI: 1.21–1.54, P = 2.30E-07), whereas FES was protective against CHD (OR = 0.68, 95% CI: 0.59–0.79, P = 6.40E-07) and MI (OR = 0.65, 95% CI: 0.54–0.77, P = 5.38E-07). Further validation through enrichment and single-cell analysis confirmed the causal effects of these proteins. Moreover, MR analysis of cardiovascular risk factors, Phe-MR, and PPI network provided insights into the potential drug development based on the proteins. Conclusions This study investigated the causal pathways associated with CHD and MI, highlighting the protective and risk roles of FES and PCSK9, respectively. FES. Specifically, the results showed that these proteins are promising therapeutic targets for future drug development.

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Section: Discussionmentioning

confidence: 99%

Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

Sun,

Yun,

Lin

et al. 2024

J Transl Med

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“…Эффективность МАТ в снижении ХС-ЛНП, выраженная в средней разнице между исходным значением и конечным, для алирокумаба составляет 51,29%, для эволокумаба -53,99% [84]. Эти данные были получены в метаанализе 45 РКИ длительностью от 8 до 134 нед.…”

Section: Discussionunclassified

New opportunities for lowering low-density lipoprotein cholesterol: comparative characteristics of PCSK9-targeted therapy

Zyryanov

Бутранова

2022

Russ J Cardiol

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The spread of cardiovascular diseases has the nature of an epidemic, which is enhanced by lipid profile disorders, manifested by hypercholesterolemia. Numerous conventional pharmacological tools for lowering cholesterol associated with low density lipoproteins do not make it possible to achieve target values in various categories of patients. Inhibition of proprotein convertase subtilisin/ kexin type 9 (PCSK9) is a promising target in the management of patients with atherosclerotic diseases and includes two main tools — monoclonal antibodies (Alirocumab and Evolocumab) and a small interfering RNA drug (Inclisiran). The presented review is devoted to a comparative analysis of the efficacy and safety of drugs from these groups.

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“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells, alirocumab and evolocumab bind selectively to circulating PCSK9, preventing its interaction with the LDL receptor [14,39]. PCSK9 inhibitors affect the entire lipid profile: could significantly reduce low-density lipoprotein cholesterol, total cholesterol, triglycerides and increase high-density lipoprotein cholesterol [15]. Many studies have noted a beneficial effect on lipid metabolism and a reduction in cardiovascular mortality [16].…”

Section: Monoclonal Antibodies Blocking Pcsk9 Actionmentioning

confidence: 99%

New drugs for the treatment of hyperlipidemia in statin-intolerant patients - review

Płonka,

Pelc,

Sitarek

et al. 2024

J Educ Health Sport

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Introduction Cardiovascular diseases are the most numerous group of diseases prevalent in the world. They are a challenge for many health systems, in terms of keeping life comfortable and also economics. The cause of selected disease entities is too much cholesterol in the blood. The most popular treatment for hypercholesterolemia is based on statins. Many patients are affected by intolerance to these drugs, so an important issue is the discovery and improvement of alternatives to statins. Purpose of work The purpose of this review is to collect literature data on the latest treatments for hypercholesterolemia with drugs other than statins and ezetimibe. Materials and methods Materials are from a review of recent literature available in PubMed. To search for articles, we used keywords such as: bempedoic acid, non-statin therapy, cardiovascular risk, inclisiran, alirocumab, cardiovascular disease, dyslipidemia, evolocumab. Summary Treatment of hypercholesterolemia with statins remains the most popular management strategy. Intolerance to treatment with these drugs creates serious clinical problems for patients. Recently, we could see the emergence of new drugs as alternatives to statins. As the results show, the new drugs can effectively replace statins in the hypolipemic treatment especially of patients who cannot be treated with them.

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Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Cardiology Journal" are listed in PubMed.

Cited by 12 publications

References 11 publications

Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

New opportunities for lowering low-density lipoprotein cholesterol: comparative characteristics of PCSK9-targeted therapy

New drugs for the treatment of hyperlipidemia in statin-intolerant patients - review

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Efficacy and safety of PCSK9 inhibition in cardiovascular disease: a meta-analysis of 45 randomized controlled trials

Abstract: This article has been peer reviewed and published immediately upon acceptance.It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Cardiology Journal" are listed in PubMed.

Cited by 12 publications

References 11 publications

​Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

​Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

New opportunities for lowering low-density lipoprotein cholesterol: comparative characteristics of PCSK9-targeted therapy

New drugs for the treatment of hyperlipidemia in statin-intolerant patients - review

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Product

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Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction

Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction