Shah Tayyab, Zhang Zhiyuan, Shah Haashim, Fanaroff Alexander C, Nathan Ashwin S, Parise Helen, Lutz John, Sugeng Lissa, Bellumkonda Lavanya, Redfors Björn, Omerovic Elmir, Petrie Mark C, Vora Amit N, Fiorilli Paul N, Kobayashi Taisei, Ahmad Yousif, Forrest John K, Giri Jay S, Herrmann Howard C, Lansky Alexandra J
The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Yale Cardiovascular Research Group, New Haven, Connecticut, USA.
Yale Cardiovascular Research Group, New Haven, Connecticut, USA.
JACC Cardiovasc Interv. 2025 Mar 24;18(6):738-748. doi: 10.1016/j.jcin.2024.11.036. Epub 2025 Feb 19.
Aortic stenosis (AS) is the leading cause of valvular heart disease-related morbidity and mortality, but there are no medical treatments to slow its progression. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have pleiotropic effects which could be disease modifying in AS.
The purpose of this study was to determine if SGLT2i usage is associated with slower progression of AS.
A target trial emulation comparing the effect of the initiation of SGLT2i compared with no SGLT2i in patients with nonsevere AS was performed using retrospective electronic medical record data from the Yale New Haven Health System from January 2016 to September 2022. Patients with native aortic valve sclerosis or nonsevere AS with at least 12 months of echocardiographic follow-up were included. Patients were excluded if they had an estimated glomerular filtration rate <30 mL/min/1.73 m or had initiated SGLT2i >1 year before the index echocardiogram. The prespecified primary outcome was progression to severe AS.
A total of 458 patients prescribed SGLT2i and 11,240 patients never prescribed SGLT2i were included. Patients were on SGLT2i for a median of 0.9 years. Patients on SGLT2i were younger and had higher rates of diabetes and chronic kidney disease. Patients on SGLT2i were more likely to have ejection fraction ≤40%. There were no differences between groups in baseline AS severity (66% sclerosis, 23% mild stenosis, and 11% moderate in overall cohort). Patients ever prescribed SGLT2i were less likely to progress to severe AS (HR: 0.61; 95% CI: 0.39-0.94; P = 0.03) with a progressively lower risk among patients on SGLT2i for >3, 6, and 12 months (HR: 0.54, 0.48, and 0.27, respectively).
This retrospective, multicenter, observational study suggests that SGLT2i may slow the progression of nonsevere AS.
主动脉瓣狭窄（AS）是心脏瓣膜病相关发病和死亡的主要原因，但尚无延缓其进展的药物治疗方法。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）具有多种效应，可能改变AS的病情。
本研究旨在确定使用SGLT2i是否与AS进展减缓相关。
利用耶鲁纽黑文医疗系统2016年1月至2022年9月的回顾性电子病历数据，进行一项目标试验模拟，比较非重度AS患者开始使用SGLT2i与未使用SGLT2i的效果。纳入有天然主动脉瓣硬化或非重度AS且有至少12个月超声心动图随访的患者。如果估计肾小球滤过率<30 mL/min/1.73 m²或在索引超声心动图前>1年开始使用SGLT2i，则排除这些患者。预先设定的主要结局是进展为重度AS。
共纳入458例使用SGLT2i的患者和11240例从未使用SGLT2i的患者。患者使用SGLT2i的中位时间为0.9年。使用SGLT2i的患者更年轻，糖尿病和慢性肾脏病的发生率更高。使用SGLT2i的患者射血分数≤40%的可能性更大。两组在基线AS严重程度方面无差异（总体队列中66%为硬化，23%为轻度狭窄，11%为中度狭窄）。曾使用SGLT2i的患者进展为重度AS的可能性较小（HR：0.61；95%CI：0.39-0.94；P = 0.03），使用SGLT2i超过3、6和12个月的患者风险逐渐降低（HR分别为0.54、0.48和0.27）。
这项回顾性、多中心、观察性研究表明，SGLT2i可能减缓非重度AS的进展。
