PT  - JOURNAL ARTICLE
AU  - Sahmin Lee
AU  - Seung-Ah Lee
AU  - Bongkun Choi
AU  - Ye-Jee Kim
AU  - Soo Jin Oh
AU  - Hong-Mi Choi
AU  - Eun Kyoung Kim
AU  - Dae-Hee Kim
AU  - Goo-Yeong Cho
AU  - Jong-Min Song
AU  - Seung Woo Park
AU  - Duk-Hyun Kang
AU  - Jae-Kwan Song
TI  - Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis
AID  - 10.1136/heartjnl-2020-317024
DP  - 2020 Sep 11
TA  - Heart
PG  - heartjnl-2020-317024
4099  - http://heart.bmj.com/content/early/2020/09/11/heartjnl-2020-317024.short
4100  - http://heart.bmj.com/content/early/2020/09/11/heartjnl-2020-317024.full
AB  - Objective To evaluate whether the use of dipeptidyl peptidase-4 (DPP-4) inhibitors and their cardiac tissue distribution profile and anticalcification abilities are associated with risk of aortic stenosis (AS) progression.Methods Out of the five different classes of DPP-4 inhibitors, two had relatively favourable heart to plasma concentration ratios and anticalcification ability in murine and in vitro experiments and were thus categorised as ‘favourable’. We reviewed the medical records of 212 patients (72±8 years, 111 men) with diabetes and mild-to-moderate AS who underwent echocardiographic follow-up and classified them into those who received favourable DPP-4 inhibitors (n=28, 13%), unfavourable DPP-4 inhibitors (n=69, 33%) and those who did not receive DPP-4 inhibitors (n=115, 54%).Results Maximal transaortic velocity (Vmax) increased from 2.9±0.3 to 3.5±0.7 m/s during follow-up (median, 3.7 years), and the changes were not different between DPP-4 users as a whole and non-users (p=0.143). However, the favourable group showed significantly lower Vmax increase than the unfavourable or non-user group (p=0.018). Severe AS progression was less frequent in the favourable group (7.1%) than in the unfavourable (29.0%; p=0.03) or the non-user (29.6%; p=0.01) group. In Cox regression analysis after adjusting for age, baseline renal function and AS severity, the favourable group showed a significantly lower risk of severe AS progression (HR 0.116, 95% CI 0.024 to 0.551, p=0.007).Conclusions DPP-4 inhibitors with favourable pharmacokinetic and pharmacodynamic properties were associated with lower risk of AS progression. These results should be considered in the preparation of randomised clinical trials on the repositioning of DPP-4 inhibitors.