TY - JOUR
T1 - Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria
AU - Sarraju, Ashish
AU - Bakris, George
AU - Cannon, Christopher P.
AU - Cherney, David
AU - Damaraju, C. V.
AU - Figtree, Gemma A.
AU - Gogate, Jagadish
AU - Greene, Tom
AU - Heerspink, Hiddo J.L.
AU - Januzzi, James L.
AU - Neal, Bruce
AU - Jardine, Meg J.
AU - Blais, Jaime
AU - Kosiborod, Mikhail
AU - Levin, Adeera
AU - Lingvay, Ildiko
AU - Weir, Matthew R.
AU - Perkovic, Vlado
AU - Mahaffey, Kenneth W.
N1 - Publisher Copyright:
© 2022
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m2) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m2, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria.
AB - Background: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Objectives: The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Methods: Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m2) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. Results: A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m2, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Conclusions: Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria.
KW - SGLT2 inhibitor
KW - canagliflozin
KW - cardiovascular outcomes
KW - diabetes
KW - heart failure
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U2 - 10.1016/j.jacc.2022.08.772
DO - 10.1016/j.jacc.2022.08.772
M3 - Article
C2 - 36302584
AN - SCOPUS:85139879629
SN - 0735-1097
VL - 80
SP - 1721
EP - 1731
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 18
ER -