Prata Alonzo Armani, Katsuyama Eric Shih, Scardini Pedro Gabriel, Covre Ana Carolina, Neto Wilson Falco, Fernandes Julia Marques, Barbosa Gabriel Scarpioni, Fukunaga Chris, Pinheiro Rafael Petri, Antunes Vanio L J, Gioli-Pereira Luciana, Fernandes Fabio
Federal University of Espírito Santo (UFES) - Campus Maruípe, Avenida Marechal Campos, 1468, Vitória, ES, 29043-900, Brazil.
Department of Medicine, FMABC University Centre, São Paulo, Brazil.
BMC Cardiovasc Disord. 2025 Apr 18;25(1):296. doi: 10.1186/s12872-025-04653-4.
Transthyretin (TTR) Cardiomyopathy (ATTR-CM) is characterized by the deposition of misfolded TTR monomers in the heart, leading to progressive heart failure. TTR-specific therapies offer a pharmacological approach to slow disease progression. However, there remains limited data on the efficacy, comparative effectiveness, and safety of these therapies. Therefore, we aim to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TTR-specific therapies with placebo in patients with ATTR-CM.
We searched through Pubmed, Cochrane, and Embase databases. Our primary outcome was: (1) All Cause Mortality. We also performed a subgroup analysis comparing TTR stabilizers versus TTR knock-down therapies (RNA inhibitors and antisense oligonucleotides).
Nine RCTs were included, involving 2,713 patients, of whom 1,160 (59.34%) were assigned to the TTR-specific therapies group. In the pooled analysis, TTR-specific therapies were associated with a significant reduction in all-cause mortality (RR 0.70; 95% CI 0.60, 0.83; p < 0.01; I² = 0%), with both TTR stabilizers and knock-down therapies showing equally effective reductions (p = 0.97). Additionally, TTR-specific therapies improved LV longitudinal strain (SMD - 0.22; 95% CI -0.34, -0.10; p < 0.01; I² = 17%) and reduced LV mass (SMD - 9.11 g; 95% CI -16.4 g, -1.82 g; p = 0.01; I² = 0%).
This meta-analysis highlights the potential of TTR-targeting therapies as an effective option for managing ATTR-CM, with significant improvements in survival. No efficacy differences were found between TTR stabilizers and knock-down therapies.
转甲状腺素蛋白（TTR）心肌病（ATTR-CM）的特征是错误折叠的TTR单体在心脏中沉积，导致进行性心力衰竭。TTR特异性疗法提供了一种减缓疾病进展的药理学方法。然而，关于这些疗法的疗效、比较有效性和安全性的数据仍然有限。因此，我们旨在对比较TTR特异性疗法与安慰剂治疗ATTR-CM患者的随机对照试验（RCT）进行系统评价和荟萃分析。
我们检索了PubMed、Cochrane和Embase数据库。我们的主要结局是：（1）全因死亡率。我们还进行了亚组分析，比较TTR稳定剂与TTR敲低疗法（RNA抑制剂和反义寡核苷酸）。
纳入了9项RCT，涉及2713例患者，其中1160例（59.34%）被分配到TTR特异性疗法组。在汇总分析中，TTR特异性疗法与全因死亡率显著降低相关（RR 0.70；95%CI 0.60，0.83；p＜0.01；I² = 0%），TTR稳定剂和敲低疗法均显示出同样有效的降低效果（p = 0.97）。此外，TTR特异性疗法改善了左心室纵向应变（SMD -0.22；95%CI -0.34，-0.10；p＜0.01；I² = 17%）并降低了左心室质量（SMD -9.11 g；95%CI -16.4 g，-1.82 g；p = 0.01；I² = 0%）。
这项荟萃分析突出了靶向TTR疗法作为管理ATTR-CM的有效选择的潜力，在生存率方面有显著改善。TTR稳定剂和敲低疗法之间未发现疗效差异。
