Byer Stefano H, Sivamurugan Aravinthasamy, Grewal Udhayvir S, Fradley Michael G, Dominic Paari
Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Am J Cardiol. 2025 May 15;243:15-18. doi: 10.1016/j.amjcard.2025.01.012. Epub 2025 Feb 6.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive form of heart failure characterized by restrictive hemodynamics and high morbidity. Tafamidis remains the only approved treatment, but its limited availability underscores the need for alternative therapies. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), shown to improve outcomes in heart failure with preserved ejection fraction (HFpEF), may offer therapeutic benefits in ATTR-CM due to shared pathophysiological mechanisms. A retrospective cohort analysis was conducted using data from the TriNetX Global Research Network. Patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) were divided into 2 groups: those receiving SGLT2i therapy and those not treated with SGLT2i. Propensity score matching balanced 19 baseline characteristics. Clinical outcomes, including heart failure exacerbations, all-cause hospitalizations, acute kidney injury (AKI), and all-cause mortality, were assessed over 5 years. The study included 623 matched patients in each cohort. SGLT2i therapy was associated with significant reductions in heart failure exacerbations (hazard ratio [HR] 0.64, 95% confidence interval [CI]: 0.48 to 0.86, p <0.01), all-cause hospitalizations (HR 0.72, 95% CI: 0.58 to 0.91, p <0.01), and AKI (HR 0.53, 95% CI: 0.35 to 0.79, p <0.01). A trend toward reduced all-cause mortality (HR 0.83, 95% CI: 0.63 to 1.08, p = 0.165) was observed, though not statistically significant. In conclusions, SGLT2 inhibitors demonstrate significant potential to reduce morbidity and healthcare utilization in wt-ATTR-CM patients, with promising trends toward improved survival. These findings highlight SGLT2i as a viable adjunct to existing therapies like tafamidis and warrant further investigation through prospective randomized trials.
转甲状腺素蛋白淀粉样变心肌病（ATTR-CM）是一种以限制性血流动力学和高发病率为特征的进行性心力衰竭形式。塔非酰胺仍然是唯一获批的治疗药物，但其供应有限凸显了寻找替代疗法的必要性。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）已被证明可改善射血分数保留的心力衰竭（HFpEF）患者的预后，由于存在共同的病理生理机制，可能对ATTR-CM具有治疗益处。利用TriNetX全球研究网络的数据进行了一项回顾性队列分析。野生型转甲状腺素蛋白淀粉样变心肌病（wtATTR-CM）患者被分为两组：接受SGLT2i治疗的患者和未接受SGLT2i治疗的患者。倾向得分匹配平衡了19项基线特征。在5年时间里评估了包括心力衰竭加重、全因住院、急性肾损伤（AKI）和全因死亡率在内的临床结局。每个队列中有623例匹配患者。SGLT2i治疗与心力衰竭加重（风险比[HR]0.64，95%置信区间[CI]：0.48至0.86，p<0.01）、全因住院（HR 0.72，95%CI：0.58至0.91，p<0.01）和AKI（HR 0.53，95%CI：0.35至0.79，p<0.01）的显著降低相关。观察到全因死亡率有降低趋势（HR 0.83，95%CI：0.63至1.08，p = 0.165），但无统计学意义。总之，SGLT2抑制剂在降低wt-ATTR-CM患者的发病率和医疗资源利用方面显示出显著潜力，在改善生存方面有令人鼓舞的趋势。这些发现突出了SGLT2i作为塔非酰胺等现有疗法的可行辅助手段，并值得通过前瞻性随机试验进一步研究。
