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J Cardiovasc Ultrasound. 2015 Dec;23(4):233-243. English. Multicenter Study.
Park HE , Jeon J , Hwang IC , Sung J , Lee SP , Kim HK , Cho GY , Sohn DW , Kim YJ .
Division of Cardiology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
Master in Statistics, Department of Statistics, Sungkyunkwan University, Seoul, Korea.
Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Division of Cardiology, Department of Internal Medicine, Sungkyunkwan University College of Medicine, Samsung Medical Center, Seoul, Korea.
Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

BACKGROUND: Anti-atherosclerotic effect of dipeptidyl peptidase-4 (DPP-4) inhibitors has been suggested from previous studies, and yet, its association with cardiovascular outcome has not been demonstrated. We aimed to evaluate the effect of DPP-4 inhibitors in reducing mortality and coronary revascularization, in association with baseline coronary computed tomography (CT). METHODS: The current study was performed as a multi-center, retrospective observational cohort study. All subjects with diabetes mellitus who had diagnostic CT during 2007-2011 were included, and 1866 DPP-4 inhibitor users and 5179 non-users were compared for outcome. The primary outcome was all-cause mortality and secondary outcome included any coronary revascularization therapy after 90 days of CT in addition to all-cause mortality. RESULTS: DPP-4 inhibitors users had significantly less adverse events [0.8% vs. 4.4% in users vs. non-users, adjusted hazard ratios (HR) 0.220, 95% confidence interval (CI) 0.102-0.474, p = 0.0001 for primary outcome, 4.1% vs. 7.6% in users vs. non-users, HR 0.517, 95% CI 0.363-0.735, p = 0.0002 for secondary outcome, adjusted variables were age, sex, presence of hypertension, high sensitivity C-reactive protein, glycated hemoglobin, statin use, coronary artery calcium score and degree of stenosis]. Interestingly, DPP-4 inhibitor seemed to be beneficial only in subjects without significant stenosis (adjusted HR 0.148, p = 0.0013 and adjusted HR 0.525, p = 0.0081 for primary and secondary outcome). CONCLUSION: DPP-4 inhibitor is associated with reduced all-cause mortality and coronary revascularization in diabetic patients. Such beneficial effect was significant only in those without significant coronary stenosis, which implies that DPP-4 inhibitor may have beneficial effect in earlier stage of atherosclerosis.

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