Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients-a description of the DAPACARD study

被引:14
作者
Akerblom, Axel [1 ,2 ]
Oldgren, Jonas [1 ,2 ]
Latva-Rasku, Aino [3 ,4 ]
Johansson, Lars [5 ]
Lisovskaja, Vera [6 ]
Karlsson, Cecilia [6 ]
Oscarsson, Jan [6 ]
Nuutila, Pirjo [3 ,4 ]
机构
[1] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden
[2] Uppsala Univ, Dept Med Sci, Uppsala, Sweden
[3] Univ Turku, Turku PET Ctr, Turku, Finland
[4] Turku Univ Hosp, Dept Endocrinol, Turku, Finland
[5] Antaros Med AB, Gothenburg, Sweden
[6] AstraZeneca, Gothenburg, Sweden
关键词
Diabetes; experimental diabetes; magnetic resonance; molecular biology; nuclear medicine; CARDIOVASCULAR OUTCOMES; HEART-FAILURE; INHIBITION; STRAIN; EMPAGLIFLOZIN; MECHANISMS; MORTALITY; DISEASE; PET;
D O I
10.1080/03009734.2018.1515281
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels. Methods: DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET). Conclusion: The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.
引用
收藏
页码:59 / 64
页数:6
相关论文
共 25 条
[1]  
[Anonymous], 2018, CIRCULATION
[2]   SGLT2 inhibitors: clinical benefits by restoration of normal diurnal metabolism? [J].
Esterline, Russell L. ;
Vaag, Allan ;
Oscarsson, Jan ;
Vora, Jiten .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2018, 178 (04) :R113-R125
[3]   Sodium-Glucose Co-transporters and Their Inhibition: Clinical Physiology [J].
Ferrannini, Ele .
CELL METABOLISM, 2017, 26 (01) :27-38
[4]   Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients [J].
Ferrannini, Ele ;
Muscelli, Elza ;
Frascerra, Silvia ;
Baldi, Simona ;
Mari, Andrea ;
Heise, Tim ;
Broedl, Uli C. ;
Woerle, Hans-Juergen .
JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (02) :499-508
[5]   Reduced Long Axis Strain Is Associated With Heart Failure and Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis [J].
Gjesdal, Ola ;
Yoneyama, Kihei ;
Mewton, Nathan ;
Wu, Colin ;
Gomes, Antoinette S. ;
Hundley, Gregory ;
Prince, Martin ;
Shea, Steven ;
Liu, Kiang ;
Bluemke, David A. ;
Lima, Joao A. C. .
JOURNAL OF MAGNETIC RESONANCE IMAGING, 2016, 44 (01) :178-185
[6]   Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction [J].
Haffner, SM ;
Lehto, S ;
Rönnemaa, T ;
Pyörälä, K ;
Laakso, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (04) :229-234
[7]   Evaluation of ECG-gated [11C] acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency [J].
Hansson, Nils Henrik ;
Tolbod, Lars ;
Harms, Johannes ;
Wiggers, Henrik ;
Kim, Won Yong ;
Hansen, Esben ;
Zaremba, Tomas ;
Frokiaer, Jorgen ;
Jakobsen, Steen ;
Sorensen, Jens .
JOURNAL OF NUCLEAR CARDIOLOGY, 2016, 23 (04) :670-679
[8]   Empagliflozin and Assessment of Lower-Limb Amputations in the EMPA-REG OUTCOME Trial [J].
Inzucchi, Silvio E. ;
Iliev, Hristo ;
Pfarr, Egon ;
Zinman, Bernard .
DIABETES CARE, 2018, 41 (01) :E4-E5
[9]   The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics [J].
Jardine, Meg J. ;
Mahaffey, Kenneth W. ;
Neal, Bruce ;
Agarwal, Rajiv ;
Bakris, George L. ;
Brenner, Barry M. ;
Bull, Scott ;
Cannon, Christopher P. ;
Charytan, David M. ;
de Zeeuw, Dick ;
Edwards, Robert ;
Greene, Tom ;
Heerspink, Hiddo J. L. ;
Levin, Adeera ;
Pollock, Carol ;
Wheeler, David C. ;
Xie, John ;
Zhang, Hong ;
Zinman, Bernard ;
Desai, Mehul ;
Perkovic, Vlado .
AMERICAN JOURNAL OF NEPHROLOGY, 2017, 46 (06) :462-472
[10]   Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction [J].
Kalam, Kashif ;
Otahal, Petr ;
Marwick, Thomas H. .
HEART, 2014, 100 (21) :1673-1680