Incidence of heart failure and renal endpoints in heart failure patients with and without severe chronic kidney disease: a nationwide real-life study of 21,959 patients
Authors: Zahir D , Madelaire C M , Fosboel E F , Kober L K , Gislason G G , Garred C G , Bonde A N B , Andersson C A , Schou M S 
Published: October 2022

Abstract

Background
Renal endpoints like end stage renal disease (ESRD) and a 50% decline in estimated glomerular filtration rate (eGFR) have been used in recent randomized clinical trials in heart failure (HF). However, the distribution of these events in larger real-life HF cohorts is unknown

Purpose
We examined the risk of traditional HF endpoints like death and worsening HF and the risk of these new renal endpoints in HF with and without severe chronic kidney disease (+/−eGFR 30 ml/min/1.73 m2) at the time of diagnosis of HF.

Methods
From nationwide registries, we identified patients receiving a diagnosis of HF from 2014–2018. Patients were included if they had creatinine available in proximity of the diagnosis (90 days before inclusion). Outcomes comprised of: (i) all-cause mortality, (ii) HF worsening, (iii) end stage renal disease and (iv) sustained 50% eGFR decline. 4-year rates of the primary outcomes were estimated using cumulative incidence function adjusted for competing risk of death, and multivariable Cox proportional hazards models were used to examine the association of covariates with a combined endpoint of the primary outcomes.

Results
We included 21,959 patients with HF and known CKD status. Median age was 73.9 years, and 7% had an eGFR &lt;30 mL/min/1.73 m2. There were few differences in baseline characteristics for patients with and without eGFR below 30. Patients with eGFR below 30 were elder and had more comorbidities. The mortality rate was 33.9% for patients with eGFR≥30 and 70.4% for patients with eGFR &lt;30. For patients with eGFR &lt;30 at the time of HF diagnosis renal outcomes were more pronounced as the first event as compared to patients with eGFR ≥30. The risk of all-cause mortality and HF hospitalization as first event was comparable between eGFR ≥30 and eGFR&lt;30 (22.7% vs 22.5% and 25.8% vs 22.5%, respectively). The risk of end-stage renal disease as first event was significantly higher for patients with eGFR &lt;30 (0.03% vs. 33.8%). The risk of a sustained 50% decline in eGFR was 4.6% for patients with eGFR ≥30 and 1.0% for patients with eGFR&lt;30 (figure 1). Across all important subgroups an eGFR &lt;30 ml/min/1.73 m2 was associated with an increased rate of the composite endpoint of death, worsening HF or a renal endpoint, and no interactions were observed (P&gt;0.01 for all) (figure 2).

Conclusion
The risks of newly introduced renal trial-endpoints in a large real-life cohort of HF patients was low compared to the risks of death or worsening HF if eGFR ≥30 ml/min/1.73 m2 at the time of diagnosis of HF. However, this pattern changed in HF patients with a eGFR &lt;30 ml/min/1.73 m2 at the time of diagnosis time of HF. The present study provides important insights into cardiorenal epidemiology in HF and have implications for planning of future trials.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Herlev/Gentofte Hospital