SGLT2 抑制剂治疗转甲状腺素蛋白淀粉样心肌病患者。

SGLT2 Inhibitor Therapy in Patients With Transthyretin Amyloid Cardiomyopathy.

机构信息

National Amyloidosis Centre, Division of Medicine, University College London, Royal Free Hospital, London, United Kingdom; Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste, Trieste, Italy; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Trieste, Italy.

Cardiomyopathy Unit, Careggi University Hospital, University of Florence, Florence, Italy; Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy.

出版信息

J Am Coll Cardiol. 2024 Jun 18;83(24):2411-2422. doi: 10.1016/j.jacc.2024.03.429.

DOI:10.1016/j.jacc.2024.03.429

PMID:38866445

Abstract

BACKGROUND

Transthyretin cardiomyopathy (ATTR-CM) was an exclusion criterion in randomized clinical trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i).

OBJECTIVES

This study sought to assess the effectiveness and tolerability of SGLT2i in patients with ATTR-CM.

METHODS

Data of 2,356 consecutive ATTR-CM patients (2014-2022) were analyzed: 260 (11%) received SGLT2i. After comparing the groups according to the treatment, 14 variables were significantly different-age and N-terminal pro-B-type natriuretic peptide were included in the model. A propensity score reflecting the likelihood of being treated with SGLT2i for each patient was determined using 16 variables.

RESULTS

The study comprised 220 patients treated with SGLT2i (age 77 ± 2 years; 82.3% wild-type ATTR-CM; left ventricular ejection fraction 45.8% ± 11%) and 220 propensity-matched control individuals. Adequacy of matching was verified (standardized differences: <0.10 between groups). Discontinuation rate for SGLT2i was 4.5%; at 12 months, SGLT2i treatment was associated with less worsening of NYHA functional class, N-terminal pro-B-type natriuretic peptide, estimated glomerular filtration rate, and fewer new initiations of loop diuretic agent therapy. Over 28 months (Q1-Q3: 18-45 months), SGLT2i therapy was associated with lower all-cause mortality (HR: 0.57; 95% CI: 0.37-0.89; P = 0.010), cardiovascular mortality (HR: 0.41; 95% CI: 0.24-0.71; P < 0.001), heart failure (HF) hospitalization (HR: 0.57; 95% CI: 0.36-0.91; P = 0.014), and the composite outcome of cardiovascular mortality and HF hospitalization (HR: 0.57; 95% CI: 0.38-0.84; P = 0.003).

CONCLUSIONS

SGLT2i treatment in ATTR-CM patients was well tolerated and associated with favorable effects on HF symptoms, renal function, and diuretic agent requirement over time. SGLT2i treatment was associated with reduced risk of HF hospitalization and cardiovascular and all-cause mortality, regardless of the ejection fraction, despite the effect size being likely overestimated. In the absence of randomized trials, these data may inform clinicians regarding the use of SGLT2i in patients with ATTR-CM.

摘要

背景

转甲状腺素蛋白心肌病（ATTR-CM）是钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）随机临床试验的排除标准。

目的

本研究旨在评估 SGLT2i 在 ATTR-CM 患者中的疗效和耐受性。

方法

分析了 2356 例连续的 ATTR-CM 患者（2014-2022 年）的数据：260 例（11%）接受了 SGLT2i 治疗。在根据治疗比较两组后，有 14 个变量存在显著差异——年龄和 N 末端脑钠肽前体被纳入模型。使用 16 个变量确定每个患者接受 SGLT2i 治疗的可能性评分。

结果

研究包括 220 例接受 SGLT2i 治疗的患者（年龄 77 ± 2 岁；82.3%野生型 ATTR-CM；左心室射血分数 45.8% ± 11%）和 220 例匹配倾向得分的对照个体。验证了匹配的充分性（组间标准化差异<0.10）。SGLT2i 的停药率为 4.5%；在 12 个月时，SGLT2i 治疗与 NYHA 心功能分级、N 末端脑钠肽前体、估计肾小球滤过率的恶化程度以及新开始使用环利尿剂治疗的情况较少有关。在 28 个月（Q1-Q3：18-45 个月）期间，SGLT2i 治疗与全因死亡率（HR：0.57；95%CI：0.37-0.89；P=0.010）、心血管死亡率（HR：0.41；95%CI：0.24-0.71；P<0.001）、心力衰竭（HF）住院率（HR：0.57；95%CI：0.36-0.91；P=0.014）和心血管死亡率和 HF 住院的复合结局（HR：0.57；95%CI：0.38-0.84；P=0.003）降低相关。

结论

在 ATTR-CM 患者中，SGLT2i 治疗耐受性良好，随着时间的推移，HF 症状、肾功能和利尿剂需求均有改善。无论射血分数如何，SGLT2i 治疗与 HF 住院和心血管及全因死亡率降低相关，这提示 SGLT2i 可能对 HF 有有益作用，尽管其作用大小可能被高估。在没有随机试验的情况下，这些数据可能为临床医生提供关于在 ATTR-CM 患者中使用 SGLT2i 的信息。