Effect of Evogliptin on the Progression of Aortic Valvular Calcification

Abstract

Background: Medical therapy for aortic stenosis (AS) remains an elusive goal. Objectives: This study sought to establish whether evogliptin, a dipeptidyl peptidase-4 inhibitor, could reduce AS progression. Methods: 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 18F-sodium fluoride positron emission tomography (18F-NaF PET). Results: 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 mm3; 95% CI: 108–163 vs 102 mm3; 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 18F-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. Conclusions: This exploratory study did not demonstrate the protective effect of evogliptin on AV calcification. Favorable 18F-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)