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American Journal of Cardiovascular... May 2024Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk....
Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
BACKGROUND
Cardiovascular disease remains a significant global health concern, with high low-density lipoprotein cholesterol (LDL-C) levels contributing to an increased risk. Familial hypercholesterolemia (FH) further complicates its management, necessitating additional lipid-lowering therapies. Evinacumab, an angiopoietin-like protein 3 monoclonal antibody, has emerged as a potential treatment, particularly for patients with FH, by effectively reducing LDL-C and triglyceride levels. This meta-analysis aimed to evaluate the efficacy and safety of evinacumab across diverse patient populations.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, relevant randomized controlled trials (RCTs) were systematically retrieved from multiple databases until November 24, 2023. The inclusion criteria were studies comparing evinacumab (at doses of 5 and 15 mg) to placebo, with outcomes focusing on lipid levels and adverse events. Standardized protocols were employed for data extraction and quality assessment, and statistical analysis was conducted using RevMan software.
RESULTS
Four RCTs, involving 270 patients, were included in the analysis. The analysis revealed significant reductions in lipid markers, particularly with the 15-mg dose of evinacumab, including triacylglycerols (standard mean difference [SMD] = -6.09, 95% confidence interval [CI] - 14.53 to 2.36, P = 0.16), total cholesterol (SMD = - 6.20, 95% CI - 11.53 to - 0.88, P = 0.02), high-density lipoprotein cholesterol (SMD = - 0.79, 95% CI - 1.27 to - 0.31, P = 0.001), LDL-C (SMD = - 4.58, 95% CI - 9.13 to - 0.03, P = 0.05), apolipoprotein (Apo) B (SMD = - 4.01, 95% CI - 7.53 to - 0.46, P = 0.03), and Apo C3 (SMD = - 7.67, 95% CI - 12.94 to - 2.41, P = 0.004). Adverse event analysis revealed no significant association, indicating good tolerability.
CONCLUSION
High-dose evinacumab (15 mg) consistently demonstrated efficacy in reducing cholesterol and other lipid markers, with favorable tolerability. Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease.
PubMed: 38713309
DOI: 10.1007/s40256-024-00649-1 -
Scientific Reports Jan 2024We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Bispecific; Intravitreal Injections; Macular Degeneration
PubMed: 38291069
DOI: 10.1038/s41598-024-52942-3 -
Blood Purification 2024Renal injury is among the leading causes of morbidity and mortality; however, there are no reliable indicators for determining the likelihood of developing chronic... (Review)
Review
INTRODUCTION
Renal injury is among the leading causes of morbidity and mortality; however, there are no reliable indicators for determining the likelihood of developing chronic kidney disease (CKD), CKD progression, or AKI events. Vascular growth factors called angiopoietins have a role in endothelial function, vascular remodeling, tissue stabilization, and inflammation and have been implicated as prognostic and predictive markers in AKI.
METHODS
Although the exact mechanism of the relationship between kidney injury and angiopoietins is unknown, this review demonstrates that AKI patients have higher angiopoietin-2 levels and that higher angiopoietin-1 to angiopoietin-2 ratio may potentially be linked with a reduced risk of the CKD progression.
RESULTS
This review therefore emphasizes the importance of angiopoietin-2 and proposes that it could be an important predictor of AKI in clinical settings.
CONCLUSION
There is a need for further large-scale randomized clinical trials in order to have a better understanding of the significance of angiopoietin-2 and for the determination of its potential clinical implications.
Topics: Humans; Biomarkers; Angiopoietin-2; Prognosis; Angiopoietin-1; Renal Insufficiency, Chronic; Acute Kidney Injury; Disease Progression
PubMed: 38262381
DOI: 10.1159/000536439 -
Nutrition Reviews Sep 2023Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils.
CONTEXT
Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils.
OBJECTIVES
To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations.
DATA SOURCES
A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population.
DATA ANALYSES
The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic).
RESULTS
In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ -7.7 mg/dL) and triglycerides (≈ -7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ -14.8 mg/dL), LDL-C (≈ -14.0 mg/dL), and non-high-density lipoprotein cholesterol (≈ -14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (-8.1 mg/dL) and LDL-C (-7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (-1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL.
CONCLUSION
Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins.
PubMed: 37695308
DOI: 10.1093/nutrit/nuad109 -
International Journal of Molecular... Aug 2023The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers... (Meta-Analysis)
Meta-Analysis Review
The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25-4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: -0.23, CI95% -0.37 to -0.09; and SMD:0.24, CI95% 0.01-0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.
Topics: Pregnancy; Female; Humans; Phosphoric Monoester Hydrolases; Angiopoietin-1; Angiopoietin-2; Pre-Eclampsia; Antibodies; Receptor, trkA
PubMed: 37629025
DOI: 10.3390/ijms241612842