In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.

Member Benefit

This content is only available year-round to ESC Professional Members, Fellows of the ESC, and Young Combined Members

Effect of dapagliflozin on cardiovascular outcomes in patients with type 2 diabetes according to baseline renal function and albuminuria status: Insights from DECLARE-TIMI 58

Session New frontiers: SGLT2 inhibitors in cardiorenal disease

Speaker Thomas Zelniker

Event : ESC Congress 2019

  • Topic : cardiovascular pharmacology
  • Sub-topic : Antidiabetic Pharmacotherapy
  • Session type : Advances in Science

Authors : TA Zelniker (Boston,US), I Raz (Jerusalem,IL), O Mosenzon (Jerusalem,IL), JP Dwyer (Nashville,US), HJL Heerspink (Groningen,NL), A Cahn (Jerusalem,IL), K Im (Boston,US), DL Bhatt (Boston,US), LA Leiter (Toronto,CA), DK Mcguire (Dallas,US), JPH Wilding (Liverpool,GB), IAM Gause-Nilsson (Gothenburg,SE), AM Langkilde (Gothenburg,SE), MS Sabatine (Boston,US), SD Wiviott (Boston,US)

Authors:
T.A. Zelniker1 , I. Raz2 , O. Mosenzon2 , J.P. Dwyer3 , H.J.L. Heerspink4 , A. Cahn2 , K. Im1 , D.L. Bhatt1 , L.A. Leiter5 , D.K. McGuire6 , J.P.H. Wilding7 , I.A.M. Gause-Nilsson8 , A.M. Langkilde8 , M.S. Sabatine1 , S.D. Wiviott1 , 1TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School - Boston - United States of America , 2Hadassah University Medical Center - Jerusalem - Israel , 3Vanderbilt University - Nashville - United States of America , 4University Medical Center Groningen - Groningen - Netherlands (The) , 5University of Toronto - Toronto - Canada , 6University of Texas Southwestern Medical School - Dallas - United States of America , 7University of Liverpool - Liverpool - United Kingdom , 8AstraZeneca - Gothenburg - Sweden ,

Topic(s):
Anti-Diabetic Pharmacotherapy

Citation:
European Heart Journal ( 2019 ) 40 ( Supplement ), 54

Background: Renal dysfunction including both reduced estimated glomerular filtration rate (eGFR) and the presence of albuminuria have each been shown to predict cardiovascular (CV) outcomes. Sodium glucose co-transporter 2 inhibitors (SGLT2i), which promote glucose excretion in the kidneys, reduce CV events and hospitalizations for heart failure (HHF) in patients with type 2 diabetes mellitus (T2DM).

Purpose: To analyze the CV efficacy of dapagliflozin according to baseline renal function and albuminuria status in DECLARE-TIMI 58.

Methods: The DECLARE-TIMI 58 trial compared dapagliflozin vs. placebo in 17,160 patients with T2DM and a creatinine clearance >60 ml/min/1.73m2 at enrollment. The dual primary endpoints were CV death/HHF and MACE (MI, stroke, CV death). We categorized patients according baseline eGFR [<60 vs. ≥60 ml/min/1.73m2 according to the CKD-EPI formula] and urinary albumin:creatinine ratio (UACR) [<30 vs. ≥30 mg/g]. Cox regression models with interaction testing were applied. The Gail-Simon test was used to test for interaction of the absolute risk differences.

Results: In total, 5198 (30.3%) patients had albuminuria (UACR 30–300: n=4029; UACR >300: n=1169) and 1265 (7.4%) had an eGFR <60 ml/min/1.73m2. Accordingly, 10958 (63.9%) patients had no manifestation of CKD, 5367 (31.3%) had either an eGFR <60 ml/min/1.73m2 or albuminuria, and 548 (3.2%) patients had both manifestations. Patients with more abnormal markers had higher event rates for CV death/HHF (KM event rates at 4 years of 3.9%, 8.3%, 17.4%) and MACE (7.5%, 11.7%, and 18.9%) for no, 1, or 2 markers of CKD, respectively. The relative risk reductions for CV death/HHF and MACE were generally consistent across the subgroups (both P-interaction >0.29), though numerically greatest (42%) in patients with reduced eGFR and albuminuria. However, the absolute risk difference increased substantially in patients with greater kidney damage (absolute risk difference of CV death/HHF: −0.5%, −1.0%, and −8.3%, respectively; P-INT for ARD 0.002; Figure). See figure for MACE and component outcomes.

Conclusions: Patients with baseline renal disease had higher rates of adverse CV outcomes. Dapagliflozin reduced events with generally consistent relative risk, but reduced the absolute risk of CVD/HHF by the greatest amount in patients with kidney disease evidenced by both reduced eGFR and albuminuria.

Member Benefit

This content is only available year-round to ESC Professional Members, Fellows of the ESC, and Young Combined Members

Get your access to resources

Join now
  • 1ESC Professional Members – access all ESC Congress resources 
  • 2ESC Association Members (Ivory, Silver, Gold) – access your Association’s resources
  • 3Under 40 or in training - with a Combined Membership, access all resources
Join now
logo esc

Our mission: To reduce the burden of cardiovascular disease

Who we are