RNA-targeting therapies for amyloid transthyretin cardiomyopathy: A systematic review and meta-analysis

IF 3.3 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Current Problems in Cardiology Pub Date : 2025-04-15 DOI:10.1016/j.cpcardiol.2025.103057

João Victor de Oliveira Ramos , João Vitor Andrade Fernandes , Yan Gadelha de Abrantes Formiga , Fabyan Esberard de Lima Beltrão , Marcelo Dantas Tavares de Melo , Fábio Fernandes

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引用次数: 0

Abstract

Introduction

Amyloid transthyretin (TTR) cardiomyopathy is a progressive disease caused by TTR amyloid deposition, leading to heart failure and mortality. RNA interference (RNAi) therapies reduce amyloid formation by silencing hepatic TTR mRNA. This meta-analysis evaluates their efficacy and safety.

Methods

A systematic search conducted in February 2025 in Cochrane Central, PubMed, and Embase identified RCTs comparing RNAi therapies with placebo. Primary outcomes were all-cause mortality and cardiac adverse events. Safety outcomes included any adverse events and serious cardiac adverse events. A leave-one-out sensitivity analysis assessed robustness. Statistical analyses used inverse-variance common-effects and DerSimonian-Laird random-effects models. Heterogeneity was evaluated using REML and I² statistics, with 95 % confidence intervals (CI).

Results

Three RCTs (1,199 patients) met inclusion criteria. RNAi therapy did not significantly reduce all-cause mortality (OR 0.97; 95 % CI 0.26–3.62; I² 72.4 %). However, excluding the ENDEAVOR trial, mortality reduction was significant (OR 0.65; 95 % CI 0.45–0.95; I² 0 %). RNAi therapy reduced cardiac adverse events in pooled (OR 0.72; 95 % CI 0.57–0.90; I² 38 %) and subgroup analyses (OR 0.66; 95 % CI 0.51–0.84; I² 0 %). No significant differences were found in serious cardiac adverse events (OR 0.98; 95 % CI 0.77–1.27; I² 0 %). Safety analyses showed no increase in overall adverse events (OR 0.78; 95 % CI 0.42–1.44; I² 49.8 %).

Conclusion

RNAi therapies reduce cardiac adverse events and may improve survival in selected patients. Further studies should refine patient selection and assess long-term outcomes.

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淀粉样转甲状腺素心肌病的rna靶向治疗：系统回顾和荟萃分析

淀粉样转甲状腺素（TTR）型心肌病是一种由TTR淀粉样沉积引起的进行性疾病，可导致心力衰竭和死亡。RNA干扰（RNAi）疗法通过沉默肝脏TTR mRNA来减少淀粉样蛋白的形成。本荟萃分析评估了它们的有效性和安全性。方法2025年2月在Cochrane Central、PubMed和Embase进行的一项系统检索确定了rct，将RNAi疗法与安慰剂进行比较。主要结局是全因死亡率和心脏不良事件。安全性结局包括任何不良事件和严重心脏不良事件。留一敏感性分析评估稳健性。统计分析使用了反方差共同效应和dersimonan - laird随机效应模型。采用REML和I²统计量评估异质性，置信区间为95%。结果3项rct（1199例）符合纳入标准。RNAi治疗没有显著降低全因死亡率(OR 0.97；95% ci 0.26-3.62；I²72.4%)。然而，排除ENDEAVOR试验，死亡率降低显著(OR 0.65；95% ci 0.45-0.95；I²0 %)。RNAi治疗可减少心脏不良事件(OR 0.72；95% ci 0.57-0.90；I²38%)和亚组分析(OR 0.66；95% ci 0.51-0.84；I²0 %)。两组在严重心脏不良事件方面无显著差异(OR 0.98；95% ci 0.77-1.27；I²0 %)。安全性分析显示总体不良事件没有增加(OR 0.78；95% ci 0.42-1.44；I²49.8%)。结论rnai治疗可减少心脏不良事件，提高患者生存率。进一步的研究应该完善患者选择和评估长期结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Problems in Cardiology 医学-心血管系统

CiteScore

4.80

自引率

2.40%

发文量

392

审稿时长

6 days

期刊介绍： Under the editorial leadership of noted cardiologist Dr. Hector O. Ventura, Current Problems in Cardiology provides focused, comprehensive coverage of important clinical topics in cardiology. Each monthly issues, addresses a selected clinical problem or condition, including pathophysiology, invasive and noninvasive diagnosis, drug therapy, surgical management, and rehabilitation; or explores the clinical applications of a diagnostic modality or a particular category of drugs. Critical commentary from the distinguished editorial board accompanies each monograph, providing readers with additional insights. An extensive bibliography in each issue saves hours of library research.