Elsevier

JACC: Heart Failure

Volume 9, Issue 11, November 2021, Pages 807-820
JACC: Heart Failure

Mini-Focus Issue: Precision Medicine: Targeted Therapies
Clinical Research
Effects of Dapagliflozin in Patients With Kidney Disease, With and Without Heart Failure

https://doi.org/10.1016/j.jchf.2021.06.017Get rights and content
Under a Creative Commons license
open access

Abstract

Objectives

The purpose of this paper was to investigate the effects of dapagliflozin in chronic kidney disease (CKD) patients, with and without heart failure (HF).

Background

Patients with CKD, with and without type 2 diabetes, were enrolled in the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial. Some patients had HF at baseline.

Methods

A total of 4,304 participants were randomized to dapagliflozin 10 mg daily or placebo. The primary composite endpoint was ≥50% decline in estimated glomerular filtration rate, end-stage kidney disease, or kidney/cardiovascular death. Secondary endpoints were a kidney composite (primary endpoint minus cardiovascular death), the composite of cardiovascular death/HF hospitalization, and all-cause death. Analysis of outcomes according to HF history was prespecified.

Results

HF patients (n = 468; 11%) were older and had more coronary disease, atrial fibrillation, and type 2 diabetes. Mean estimated glomerular filtration rate was similar in patients with and without HF. Rates of HF hospitalization/cardiovascular death and death from any cause were higher in HF patients, but the secondary kidney failure outcome occurred at the same rate in people with and without HF. Dapagliflozin reduced the risk of the primary outcome equally in patients with HF (HR: 0.58 [95% CI: 0.37-0.91]) and without HF (HR: 0.62 [95% CI: 0.51-0.75]) (P interaction = 0.59). The proportional risk-reductions were similar in patients with and without HF for the cardiovascular death/HF hospitalization composite (HR: 0.68 [95% CI: 0.44-1.05] vs HR: 0.70 [95% CI: 0.51-0.97], respectively; P interaction = 0.90), and all-cause death (HR: 0.56 [95% CI: 0.34-0.93] vs HR: 0.73 [95% CI: 0.54-0.97], respectively; P interaction = 0.39), although absolute risk reductions were larger in HF patients. Adverse event rates were low and did not differ among patients with or without HF.

Conclusions

Dapagliflozin reduced the risk of kidney failure and cardiovascular death/HF hospitalization and prolonged survival in CKD patients with or without type 2 diabetes, independently of history of HF. (A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease [DAPA-CKD]; NCT03036150)

Key Words

cardiovascular disease
chronic kidney disease
dapagliflozin
heart failure
SGLT2 inhibitor

Abbreviations and Acronyms

CKD
chronic kidney disease
eGFR
estimated glomerular filtration rate
HF
heart failure
SGLT2
sodium glucose cotransporter 2
UACR
urinary albumin-to-creatinine ratio

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