J Cardiovasc Ultrasound.  2015 Dec;23(4):233-243. 10.4250/jcu.2015.23.4.233.

Effect of Dipeptidyl Peptidase-4 Inhibitor on All-Cause Mortality and Coronary Revascularization in Diabetic Patients

Affiliations
  • 1Division of Cardiology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea.
  • 2Master in Statistics, Department of Statistics, Sungkyunkwan University, Seoul, Korea.
  • 3Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. kimdamas@snu.ac.kr
  • 4Division of Cardiology, Department of Internal Medicine, Sungkyunkwan University College of Medicine, Samsung Medical Center, Seoul, Korea.
  • 5Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Abstract

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.

Keyword

Dipeptidyl peptidase-4 inhibitor; Mortality; Cardiovascular outcome; Computed tomography

MeSH Terms

Atherosclerosis
C-Reactive Protein
Calcium
Cohort Studies
Constriction, Pathologic
Coronary Stenosis
Coronary Vessels
Diabetes Mellitus
Hemoglobin A, Glycosylated
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypertension
Mortality*
Retrospective Studies
C-Reactive Protein
Calcium

Figure

  • Fig. 1 Adjusted survival curve of DPP-4 inhibitor use for primary outcome (A) and secondary outcome (B). DPP-4: dipeptidyl peptidase-4.

  • Fig. 2 Adjusted survival curve of DPP-4 inhibitor use for primary outcome in subjects with < 50% (A) and ≥ 50% (B) stenosis at baseline computed tomography. DPP-4: dipeptidyl peptidase-4.

  • Fig. 3 Adjusted survival curve of DPP-4 inhibitor cumulative use for primary (A) and secondary outcome (B). DPP-4: dipeptidyl peptidase-4.


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