Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
J Am Coll Cardiol. 2024 Sep 17;84(12):1064-1075. doi: 10.1016/j.jacc.2024.06.037.
Medical therapy for aortic stenosis (AS) remains an elusive goal.
This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression.
A total of 228 patients (age 67 ± 11 years; 33% women) with AS were randomly assigned to receive placebo (n = 75), evogliptin 5 mg (n = 77), or evogliptin 10 mg (n = 76). The primary endpoint was the 96-week change in aortic valve calcium volume (AVCV) on computed tomography. Secondary endpoints included the 48-week change in active calcification volume measured using F-sodium fluoride positron emission tomography (F-NaF PET).
There were no significant differences in the 96-week changes in AVCV between evogliptin 5 mg and placebo (-5.27; 95% CI: -55.36 to 44.82; P = 0.84) or evogliptin 10 mg and placebo (-18.83; 95% CI: -32.43 to 70.10; P = 0.47). In the placebo group, the increase in AVCV between 48 weeks and 96 weeks was higher than that between baseline and 48 weeks (136 mm; 95% CI: 108-163 vs 102 mm; 95% CI: 75-129; P = 0.0485). This increasing trend in the second half of the study was suppressed in both evogliptin groups. The 48-week change in active calcification volume on F-NaF PET was significantly lower in both the evogliptin 5 mg (-1,325.6; 95% CI: -2,285.9 to -365.4; P = 0.008) and 10-mg groups (-1,582.2; 95% CI: -2,610.8 to -553.5; P = 0.0038) compared with the placebo group.
This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable F-NaF PET results and possible suppression of aortic valve calcification with longer medication use in the evogliptin groups suggest the need for larger confirmatory trials. (A Multicenter, Double-blind, Placebo-controlled, Stratified-randomized, Parallel, Therapeutic Exploratory Clinical Study to Evaluate the Efficacy and Safety of DA-1229 in Patients With Calcific Aortic Valve Disease; NCT04055883).
主动脉瓣狭窄（AS）的药物治疗仍然难以实现。
本研究旨在确定二肽基肽酶-4 抑制剂 evogliptin 是否能减缓 AS 进展。
共纳入 228 例 AS 患者（年龄 67 ± 11 岁；33%为女性），随机分为安慰剂组（n=75）、evogliptin 5mg 组（n=77）和 evogliptin 10mg 组（n=76）。主要终点为计算机断层扫描（CT）检查的 96 周主动脉瓣钙体积（AVCV）变化。次要终点包括氟-18 标记的氟化钠正电子发射断层扫描（F-NaF PET）测量的活性钙化体积在 48 周的变化。
与安慰剂组相比，evogliptin 5mg 组（-5.27；95%置信区间：-55.36 至 44.82；P=0.84）和 evogliptin 10mg 组（-18.83；95%置信区间：-32.43 至 70.10；P=0.47）的 96 周 AVCV 变化均无显著差异。在安慰剂组中，48 周至 96 周之间的 AVCV 增加量高于基线至 48 周之间的增加量（136mm；95%置信区间：108-163 比 102mm；95%置信区间：75-129；P=0.0485）。这种在研究后半段的增加趋势在两个 evogliptin 组中都受到抑制。F-NaF PET 测量的活性钙化体积在 evogliptin 5mg 组（-1,325.6；95%置信区间：-2,285.9 至-365.4；P=0.008）和 10mg 组（-1,582.2；95%置信区间：-2,610.8 至-553.5；P=0.0038）中均显著低于安慰剂组。
这项探索性研究并未显示 evogliptin 对主动脉瓣钙化的保护作用。F-NaF PET 结果良好，以及 evogliptin 组在更长的用药时间内可能抑制主动脉瓣钙化，提示需要更大规模的确认性试验。（一项多中心、双盲、安慰剂对照、分层随机、平行、治疗性探索性临床试验，旨在评估 DA-1229 在钙化性主动脉瓣疾病患者中的疗效和安全性；NCT04055883）。
