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 F-18-sodium fluoride positron emission tomography (F-18-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 mm(3); 95% CI: 108-163 vs 102 mm(3); 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-18-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 F-18-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) (c) 2024 by the American College of Cardiology Foundation.