Evinacumab 345mg/2.3ml solution for infusion vials

Background: Direct comparisons between the drugs are limited, and the dosing remains debatable. Therefore, the study aims to indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis. Methods: Databases including PubMed, EMBASE, Web of Science, and the Cochrane Library were utilized to retrieve randomized controlled trials (RCTs). The search was conducted up to July 1, 2023. The Cochrane risk of bias tool was employed to appraise the quality of included studies. R software was used to conduct the Bayesian network meta-analysis. Results: Twenty-one RCTs with 10,835 patients were included. The network meta-analysis indicated that Evolocumab [mean difference (MD) = -60, 95% credibility interval (CrI) (-72, -49)] was the most effective (87%) in reducing low-density lipoprotein cholesterol (LDL-C), followed by alirocumab (71.4%) and inclisiran (47.2%), with placebo being the least effective (0.01%). In increasing high-density lipoprotein cholesterol (HDL-C), evolocumab [MD = 6.5, 95% CrI (3.2, 10)] ranked first (81.8%), followed by alirocumab (68.2%), with placebo again at the bottom (0.03%). In lowering total cholesterol, evolocumab [MD = -36, 95% CrI (-54, -19)] performed the best (86%), followed by alirocumab (64%), and placebo remained the least effective (0.04%). Regarding adverse events (AEs), evinacumab [odds ratio (OR) = 2, 95% CrI (1.17, 3.44)] ranked the highest (98.9%), followed by inclisiran (59.6%) and evolocumab (15.2%). Conclusions: Evolocumab appears to be the most effective in increasing HDL-C and reducing LDL-C and total cholesterol. Evinacumab shows the best safety profile with the lowest incidence of AEs. The PROSPERO registration: CRD42024570445, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=570445.

Abstract licence: CC BY 4.0

AimsInhibition of angiopoietin-like protein 3 (ANGPTL3) has been proposed as a promising approach to reduce residual cardiovascular risk. We conducted a meta-analysis of randomized controlled trials (RCTs) to provide a comprehensive evaluation of the metabolic effects of ANGPTL3 inhibitors.MethodsDatabases (PubMed, EMBASE, Web of Science, CENTRAL, ClinicalTrials.gov) were searched from inception to July 2025. Eligible studies were RCTs comparing ANGPTL3 inhibitors against placebo. Outcomes included triglycerides (TG), LDL-C, apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), very-low-density lipoprotein cholesterol (VLDL-C), apolipoprotein A1 (ApoA1), apolipoprotein C3 (ApoC3), lipoprotein(a) (Lp(a)), remnant cholesterol (RC), ANGPTL3 and C-reactive protein (CRP). Pooled estimates of percentage change from baseline were obtained using fixed- and random-effects models. Subgroup analysis was performed based on the mechanism of action: monoclonal antibodies (mAbs, evinacumab), antisense oligonucleotides (ASOs, vupanorsen), and small interfering RNAs (siRNA, zodasiran and solbinsiran).ResultsNine RCTs (1,254 participants) were included. ANGPTL3 inhibition significantly reduced TG (-47.1%), LDL-C (-21.6%), ApoB (-19.9%), non-HDL-C (-31.5%), TC (-32.8%), VLDL-C (-40.6%), and RC (-72.7%). Modest but consistent reductions were also observed in Lp(a) (-11.5%), ApoA1 (-18.3%), and ApoE (-16.4%). ANGPTL3 inhibitors markedly reduced circulating ANGPTL3 protein (-70.7%), with no significant effect on high-sensitivity CRP. Subgroup analyses demonstrated greater reductions in LDL-C, ApoB, non-HDL-C, and TC with evinacumab compared to the other groups, whereas small interfering RNAs produced more pronounced VLDL-C lowering compared with vupanorsen.ConclusionsANGPTL3 inhibition offers broad lipid-lowering benefits, with particularly marked reductions in TG-rich lipoproteins.

Abstract licence: CC BY

Abstract Purpose To indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis. Methods Randomized controlled trials (RCTs) were retrieved from databases including PubMed, EMBASE, Web of Science, and Cochrane Library. The search was conducted up to July 1, 2023. The quality of included studies was assessed using the Cochrane risk of bias tool, and data analysis was performed using R software. Results A total of 21 randomized controlled trials involving 10,835 patients were included. The network meta-analysis indicated that Evolocumab was the most effective (87%) in reducing low-density lipoprotein cholesterol (LDL-C), followed by alirocumab (71.4%) and inclisiran (47.2%), with placebo being the least effective (0.01%). In increasing high-density lipoprotein cholesterol (HDL-C), evolocumab ranked first (81.8%), followed by alirocumab (68.2%), with placebo again at the bottom (0.03%). In lowering total cholesterol, evolocumab performed the best (86%), followed by alirocumab (64%), and placebo remained the least effective (0.04%). Regarding adverse events (AEs), evinacumab ranked the highest (98.9%), followed by inclisiran (59.6%) and evolocumab (15.2%). Conclusion Evolocumab appears to be the most effective in increasing HDL-C, and reducing LDL-C and total cholesterol. Evinacumab shows the best safety profile with the lowest incidence of AEs.

Abstract licence: CC BY 4.0