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Rev Cardiovasc Med. 2018 Jun 30;19(2):41-49. doi: 10.31083/j.rcm.2018.02.907.

Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review.

Author information

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.

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.

KEYWORDS:

CANVAS; EMPAREG OUTCOME; DECLARETIMI 58; SGLT-2 inhibitor; canagliflozin; dapagliflozin; empagliflozin; ertugliflozin; sotagliflozin

PMID:
31032602
DOI:
10.31083/j.rcm.2018.02.907
[Indexed for MEDLINE]
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Conflict of interest statement

The authors declare no competing interests.

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