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Reviews in Cardiovascular Medicine  2018, Vol. 19 Issue (2): 41-49     DOI: 10.31083/j.rcm.2018.02.907
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Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review
Aaron Y. Kluger1, 2, *(), Kristen M. Tecson1, 2, 3, Clay M. Barbin4, 5, Andy Y. Lee4, 5, Edgar V. Lerma6, Zachary P. Rosol4, 5, Janani Rangaswami7, 8, Norman E. Lepor9, 10, Michael E. Cobble11, Peter A. McCullough1, 3, 4, 5
1 Baylor Heart and Vascular Institute, Dallas, TX, 75226
2 Baylor Scott & White Research Institute, Dallas, TX, 75226
3 Texas A & M College of Medicine Health Science Center, Dallas, TX, 75226
4 Baylor University Medical Center, Dallas, TX, 75226
5 Baylor Heart and Vascular Hospital, Dallas, TX, 75226
6 UIC/Advocate Christ Medical Center, Oak Lawn, IL, 60453
7 Einstein Medical Center, Philadelphia, PA, 19141
8 Sidney Kimmel College of Thomas Jefferson University, Philadelphia, PA, 19107
9 David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095
10 Cedars-Sinai Medical Center, Los Angeles, CA, 90048
11 University of Utah School of Medicine, Salt Lake City, UT, 84132
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Abstract:
In this systematic review, we sought to summarize the 3 recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials (Dapagliflozin Effect on CardiovasculAR Events (DECLARE-TIMI 58), Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, and Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)) and to explore the potential causes for their different results. We found that the major adverse cardiovascular event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14% for DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME, respectively. DECLARETIMI 58 had the fewest cardiorenal events (across treatment and control arms) and EMPA-REG OUTCOME the most. DECLARE-TIMI 58 used alternative inclusion criterion for baseline renal function (creatinine clearance ≧ 60 mL/min) compared to the other trials (estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 bodysurface area). Therefore, the DECLARE-TIMI 58 study cohort had higher eGFR (mean eGFR 85.2 mL/min/1.73 m2 compared to 76.5 and 74 in CANVAS and EMPAREG OUTCOME, respectively); this may have caused the difference in results. Additionally contributing to the high event rate in EMPA-REG OUTCOME was the requirement of prior confirmed cardiovascular disease (CVD), resulting in 99.2% of patients with CVD compared to only 65.6% and 40.6% in CANVAS and DECLARE-TIMI 58, respectively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.
Key words:  SGLT-2 inhibitor      empagliflozin      canagliflozin      dapagliflozin      ertugliflozin      sotagliflozin      CANVAS      EMPAREG OUTCOME      DECLARETIMI 58     
Published:  30 June 2018     
*Corresponding Author(s):  Aaron Y. Kluger, E-mail: aaron.kluger@bswhealth.org   

Cite this article: 

Aaron Y. Kluger, Kristen M. Tecson, Clay M. Barbin, Andy Y. Lee, Edgar V. Lerma, Zachary P. Rosol, Janani Rangaswami, Norman E. Lepor, Michael E. Cobble, Peter A. McCullough. Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review. Reviews in Cardiovascular Medicine, 2018, 19(2): 41-49.

URL: 

https://rcm.imrpress.com/EN/10.31083/j.rcm.2018.02.907     OR     https://rcm.imrpress.com/EN/Y2018/V19/I2/41

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