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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.
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INTRODUCTION: In patients with non-valvular atrial fibrillation (NVAF), mechanical occlusion of the left atrial appendage (LAA) using a permanently implanted device may be an effective alternative to oral anti-coagulants (OAC). To facilitate left atrial appendage closure (LAAC), multiple percutaneous devices have been proposed. Watchman Generation 2.5 and Amplatzer Amulet are the two most popular used devices for preventing stroke in patients with NVAF. We sought to compare safety and efficacy outcomes between Watchman 2.5 and Amplatzer Amulet in patients undergoing LAAC procedure. METHODS: We carried out a comprehensive and systematic search of the databases PubMed and Scopus, for all studies that compared the safety and efficacy of Watchman 2.5 and Amplatzer Amulet devices, from inception, till June 2023. We performed the statistical analysis using Review Manager (V.5.4.1 Cochrane Collaboration, London, United Kingdom). The safety outcomes of interest included device success, device-related thrombus, device embolization perioperatively and at follow-up, perioperative pericardial perfusion events, and perioperative cardiac tamponade events. Efficacy outcomes were all-cause mortality perioperatively and at follow-up, cardiovascular (CV) mortality at follow-up, stroke, major and minor bleeding events at follow-up, transient ischemic attack (TIA) in follow-up period, thromboembolic events in follow-up period, and peri-device leakage in perioperative period. All data was analysed using a random-effects model, and presented as risk ratios (RRs) with 95% confidence intervals (95%CIs). RESULTS: Regarding safety outcomes, device success was non-significantly reduced in Watchman group when compared with Amulet (RR 0.99, p = 0.57; I2 = 34%). In contrast, device-related thrombus was non-significantly increased in Watchman 2.5 group in comparison to Amulet (RR 1.44, p = 0.11; I2 = 0%). There was no significant difference between the devices in terms of device embolization in the perioperative (RR 0.36, p = 0.38; I2 = 22%) and follow-up (RR 2.24, p = 0.13; I2 = 0%) periods. Likewise, there was no significant difference in the risks of pericardial effusion (RR 0.98, p = 0.98; I2 = 0%), and cardiac tamponade (RR 0.65, p = 0.76; I2 = 62%) perioperatively. Regarding efficacy outcomes, no significant difference was observed in all-cause mortality between devices perioperatively (RR 0.51, p = 0.32; I2 = 0%) and at follow-up (RR 1.08, p = 0.56; I2 = 0%). CV-mortality was non-significantly reduced in Watchman group when compared with Amulet (RR 0.57, p = 0.20; I2 = 0%). The Amulet device was not superior to the Watchman device in terms of stroke at follow-up (RR 1.13, p = 0.63; I2 = 0%). Sub-group analysis showed comparable ischaemic and haemorrhagic stroke events between two devices. Furthermore, at follow-up, there was no significant difference in major (RR 1.06, p = 0.63; I2 = 0%) and minor bleeding events (RR 1.81, p = 0.17; I2 = 0%) between the two devices. No difference was observed for trans-ischemic attack (RR 1.89, p = 0.24; I2 = 0%) and thromboembolic events (RR 0.96, p = 0.96; I2 = 0%) at follow-up. No significant difference was observed between devices for peri-device leakage in perioperative period (RR 2.16, p = 0.05; I2 = 0%). CONCLUSION: The data suggested that LAAC is safe and efficacious procedure irrespective of device used, with generally low complication rates. Watchman generation 2.5 remains non-superior to Amplatzer Amulet in terms of safety and efficacy outcomes.
