Tsuyoshi Nozue1, Kazuki Fukui2, Takeshi Takamura3, Takashi Sozu4, Kiyoshi Hibi5, Satoru Kishi6, Ichiro Michishita7. 1. Division of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Yokohama, Japan. Electronic address: nozue2493@yahoo.co.jp. 2. Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan. 3. Department of Cardiology, Nagatsuda Kosei General Hospital, Yokohama, Japan. 4. Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan. 5. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. 6. Cardiocore Japan, Tokyo, Japan. 7. Division of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Yokohama, Japan.
Abstract
BACKGROUND: Patients with type 2 diabetes are at high risk for developing coronary artery disease (CAD). Noninvasive anatomic assessment by coronary computed tomography angiography (CCTA) is being increasingly used for detecting or excluding CAD. Recently, fractional flow reserve (FFR) using routinely acquired CCTA datasets (FFRCT) has been developed. Although intensive glycemic control can reduce the risk of microvascular complications, intensive glucose control does not seem to be beneficial in preventing major cardiovascular events when compared with standard therapy. However, it has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. In addition, DPP-4 inhibitors attenuate the progression of carotid intima-media thickness in patients with type 2 diabetes. Therefore, this study will be performed to evaluate the effects of alogliptin, a DPP-4 inhibitor, on coronary atherosclerosis using FFRCT in patients with type 2 diabetes. METHODS AND DESIGN: This study will be a prospective, non-randomized, multicenter trial performed in Japan. Patients with type 2 diabetes who have intermediate coronary artery stenosis (diameter stenosis <70%) as evaluated by CCTA will be treated with 25mg/day of alogliptin. After 48 weeks' treatment, CCTA will be repeated. The primary endpoint will be changes in FFRCT, and the secondary endpoint will be the change in plaque volume from baseline to the 48-week follow-up. CONCLUSION: This study will be the first multicenter trial to evaluate the effects of alogliptin on coronary atherosclerosis using the newly developed FFRCT as the primary endpoint, and the findings will clarify the anti-atherogenic effects of alogliptin.
BACKGROUND:Patients with type 2 diabetes are at high risk for developing coronary artery disease (CAD). Noninvasive anatomic assessment by coronary computed tomography angiography (CCTA) is being increasingly used for detecting or excluding CAD. Recently, fractional flow reserve (FFR) using routinely acquired CCTA datasets (FFRCT) has been developed. Although intensive glycemic control can reduce the risk of microvascular complications, intensive glucose control does not seem to be beneficial in preventing major cardiovascular events when compared with standard therapy. However, it has been reported that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherogenic effects in an animal model. In addition, DPP-4 inhibitors attenuate the progression of carotid intima-media thickness in patients with type 2 diabetes. Therefore, this study will be performed to evaluate the effects of alogliptin, a DPP-4 inhibitor, on coronary atherosclerosis using FFRCT in patients with type 2 diabetes. METHODS AND DESIGN: This study will be a prospective, non-randomized, multicenter trial performed in Japan. Patients with type 2 diabetes who have intermediate coronary artery stenosis (diameter stenosis <70%) as evaluated by CCTA will be treated with 25mg/day of alogliptin. After 48 weeks' treatment, CCTA will be repeated. The primary endpoint will be changes in FFRCT, and the secondary endpoint will be the change in plaque volume from baseline to the 48-week follow-up. CONCLUSION: This study will be the first multicenter trial to evaluate the effects of alogliptin on coronary atherosclerosis using the newly developed FFRCT as the primary endpoint, and the findings will clarify the anti-atherogenic effects of alogliptin.