Does Evolocumab, as a PCSK9 Inhibitor, Ameliorate the Lipid Profile in Familial Hypercholesterolemia Patients? A Meta-Analysis of Randomized Controlled Trials

Eslami, Seyyed Majid; Nikfar, Shekoufeh; Ghasemi, Maryam; Abdollahi, Mohammad

doi:10.18433/j36c8n

Cited by 12 publications

(7 citation statements)

References 35 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among these studies, there were two in FH patients. However, one report studied the role and safety of evolocumab but did not include alirocumab [ 33 ]. In another study, although the role and safety of PCSK9-mAbs, including evolocumab and alirocumab, were discussed, the patients with FH were controversial because the data extracted by the authors did not exclude the non-FH patients included in the clinical study [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] A Systematic Review and Meta‐Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

Zhu

Zeng

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

Objectives. The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9-mAbs in the treatment of familial hypercholesterolemia (FH). Methods. A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration’s tool, and publication bias was evaluated by a contour-enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta-analysis was performed using R software, version 4.0.3. Results. A meta-analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9-mAbs reduced the LDL-C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9-mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein-B (Apo-B), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and increased HDL-C and apolipoprotein-A1 (Apo-A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion. PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

[Retracted] A Systematic Review and Meta‐Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

Zhu

Zeng

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Currently available data have demonstrated fewer untoward muscle-related adverse effects as well as greater LDL-C reductions in statin-intolerant patients administered with the fully monoclonal antibody to PCSK9 ( Moriarty et al, 2015 ; Nissen et al, 2016 ). Findings from a meta-analysis of randomized controlled trials have indicated that evolocumab could be a hopeful agent for challenging patients, such as those having statin intolerance or patients who fail to attain the target goal of LDL-C despite consumption of maximum doses of statins ( Eslami et al, 2017 ). Our results suggest that DXXK, a marketed product commonly used in atherosclerotic CAD, has good clinical value and may support statin action due to the reversal of PCSK9/LDLR expression in ApoE –/– mice revealed in our study.…”

Section: Discussionmentioning

confidence: 99%

Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9

Gao

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

Numerous risk factors are responsible for the development of atherosclerosis, for which an increased serum level of low-density lipoprotein cholesterol (LDL-C) is a driving force. By binding to the low-density lipoprotein cholesterol receptor (LDLR) and inducing LDLR degradation, proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis regulation. The inducement of PCSK9 expression is also an important reason for statin intolerance. The Di’ao Xinxuekang (DXXK) capsule extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product used in atherosclerotic cardiovascular disease. Although DXXK has been widely used in atherosclerotic cardiovascular treatment for nearly 30 years, studies on the potential mechanisms of the lipid-lowering effect are very limited. The purpose of the present study was to demonstrate the possible involvement of the PCSK9/LDLR signaling pathway in the lipid-lowering and antiatherosclerotic effect of DXXK in high-fat diet-fed ApoE–/– mice. The results showed that DXXK treatment alleviated hyperlipidemia, fat accumulation, and atherosclerosis formation in ApoE–/– mice. Furthermore, changes in the expression of PCSK9 mRNA in liver tissue and the circulating PCSK9 level in ApoE–/– mice were both reversed after DXXK treatment, and upregulation of LDLR in the liver was also detected in the protein level in DXXK-treated mice. Our study is the first to show that DXXK could alleviate lipid disorder and ameliorate atherosclerosis with downregulation of the PCSK9 in high-fat diet-fed ApoE–/– mice, suggesting that DXXK may be a potential novel therapeutic treatment and may support statin action in the treatment of atherosclerosis.

show abstract

“…By combining with the epidermal growth factor-like repeat A domain (EGF-A) of low-density lipoprotein receptor (LDLR) and lowing the recycling of LDLR to cell surface, PCSK9 mediates serum LDL-C levels. Recently, several PCSK9 inhibitors, such as alirocumab and evolocumab, were applied in patients with familial hypercholesterolemia and/or CAD in different countries, and were verified to decrease total cholesterol (TC), LDL-C, triglyceride (TG) and the ratio of TC to high-density lipoprotein cholesterol (HDL-C) greatly [6].…”

Section: Introductionmentioning

confidence: 99%

Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population

et al. 2018

View full text Add to dashboard Cite

BackgroundGenetic and environment factors affect the occurrence and development of coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9 (PCSK9), has been investigated extensively in the field of lipid metabolism and CAD. We performed this case-control study to investigate the relationship between serum PCSK9 levels and PCSK9 polymorphisms and lipid levels and CAD risk in a southern Chinese population.MethodsA hospital-based case-control study with 1, 096 subjects, including 626 CAD patients and 470 controls, were conducted. Genotyping of PCSK9 polymorphisms was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR) method.ResultsThe frequencies of the AA, AG and GG genotypes of PCSK9 E670G polymorphism were 90.58, 9.27, and 0.16% in the CAD patients, compared with 88.72, 10.85 and 0.43% in the controls, respectively. No R46L variant was detected in this population. There were no significant differences in genotype and allele frequencies of PCSK9E670G polymorphism between the CAD group and the controls. Serum lipid levels were not significantly different in carriers with the G allele and those with the AA genotype. The median (QR) of PCSK9 concentration was 1205.00 ng/l (577.28–1694.13 ng/l) in cases and 565.87 ng/l (357.17–967.50 ng/l) in controls, respectively. Compared with controls, CAD patients had significantly higher PCSK9 levels (z = 4.559, P < 0.001). After adjusting for age, gender, essential hypertension, diabetic mellitus, smoking and lipid profiles, PCSK9 levels remain significantly associated with increased CAD susceptibility (OR = 1.002, 95% CI = 1.001–1.002, P < 0.001). The correlation analyses showed that serum PCSK9 levels were positively associated with triglyceride (TG), Apo B and atherogenic index of plasma (AIP) levels in controls. No significant association between the PCSK9 E670G polymorphism and serum PCSK9 levels was observed in the CAD group and the controls.ConclusionsThe present study shows that serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk in Southern Chinese Han population, and that serum PCSK9 levels are positively associated with AIP.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0859-5) contains supplementary material, which is available to authorized users.

show abstract

Does Evolocumab, as a PCSK9 Inhibitor, Ameliorate the Lipid Profile in Familial Hypercholesterolemia Patients? A Meta-Analysis of Randomized Controlled Trials

Cited by 12 publications

References 35 publications

[Retracted] A Systematic Review and Meta‐Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

[Retracted] A Systematic Review and Meta‐Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9

Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population

Contact Info

Product

Resources

About