Impact of early intervention with alogliptin on coronary plaque regression and stabilization in patients with acute coronary syndromes

Abstract

Background and aims

Anti-atherosclerotic effects of early intervention with dipeptidyl peptidase-4 inhibitors remain poorly defined.

Methods

In a prospective, single-center, randomized trial, 66 patients with acute coronary syndrome (ACS) and mild dysglycemia (HbA1c 6.0 (5.7, 6.3)%, 58% of impaired glucose tolerance) were randomly assigned to receive alogliptin (n = 33) or placebo (n = 33) in addition to standard treatments. Serial intravascular ultrasound (IVUS) was performed at baseline and 10 months to evaluate changes in coronary percent plaque volumes (%PV) and plaque tissue components of non-culprit lesions (NCLs).

Results

Baseline clinical and IVUS characteristics, as well as decreases in HbA1c and lipid variables during 10 months, did not differ significantly between the 2 groups. In contrast, with respect to vascular responses, the alogliptin group showed significantly greater decreases in plaque volumes (−0.3 ± 0.6 vs. −0.04 ± 0.7 mm³/mm, p = 0.03) and %PV (−0.9 ± 2.8 vs. 1.2 ± 3.6%, p = 0.01), with a tendency toward smaller lumen loss (−0.1 ± 0.7 vs. −0.4 ± 0.8 mm³/mm, p = 0.07) compared with the placebo group. Significantly decreased percent necrotic volumes (%NV) (−1.9 ± 3.8 vs. 0.3 ± 3.7%, p = 0.03) and increased fibrotic volumes (2.5 ± 5.0 vs. −0.3 ± 5.3%, p = 0.05) were or tended to be seen in alogliptin versus placebo groups at 10 months. In multiple regression analysis, alogliptin use was a statistically significant determinant of changes in %PV (β = −0.33, p = 0.004) and %NV (β = −0.28, p = 0.03) at 10 months.

Conclusions

Alogliptin treatment, independently of glycemic and lipid status, resulted in significant plaque regression and stabilization in NCLs in patients with ACS and mild dysglycemia, suggesting the potential utility of early intervention with incretin-based treatments for this patients' subset.