Abstract
Aims Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. Methods and results DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200–5000mg/g and an estimated glomerular filtration rate (eGFR) 25–75mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. Conclusion In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1216-1227 |
| Number of pages | 12 |
| Journal | European heart journal |
| Volume | 42 |
| Issue number | 13 |
| DOIs | |
| State | Published - Apr 1 2021 |
Keywords
- Chronic kidney disease
- Dapagliflozin
- SGLT2 inhibitor
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
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In: European heart journal, Vol. 42, No. 13, 01.04.2021, p. 1216-1227.
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TY - JOUR
T1 - Effects of dapagliflozin on mortality in patients with chronic kidney disease
T2 - A pre-specified analysis from the DAPA-CKD randomized controlled trial
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N1 - Publisher Copyright: © The Author(s), 2021.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Aims Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. Methods and results DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200–5000mg/g and an estimated glomerular filtration rate (eGFR) 25–75mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. Conclusion In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
AB - Aims Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. Methods and results DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200–5000mg/g and an estimated glomerular filtration rate (eGFR) 25–75mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. Conclusion In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
KW - Chronic kidney disease
KW - Dapagliflozin
KW - SGLT2 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85103743786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103743786&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehab094
DO - 10.1093/eurheartj/ehab094
M3 - Article
C2 - 33792669
AN - SCOPUS:85103743786
SN - 0195-668X
VL - 42
SP - 1216
EP - 1227
JO - European heart journal
JF - European heart journal
IS - 13
ER -