Association between the risk of heart failure hospitalization and end-stage renal disease with digoxin usage in patients with cardiorenal syndrome: A population-based study

Abstract

BackgroundThe management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort.MethodWe conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD).ResultsThe all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09–1.46, p = 0.002). In a subgroup analysis, there was significantly high mortality in the 0.26–0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23–1.82, p<0.001). Thus, the p for trend was 0.013. With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05–1.30, p = 0.004], especially in the >0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01–1.41, p = 0.046; p for trend = 0.006). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63–0.99, p = 0.048). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16–1.54, p<0.001). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26–0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06–1.66, p = 0.015; sHR = 1.44; 95% CI = 1.18–1.75; p for trend<0.001).ConclusionDigoxin should be prescribed with caution to patients with CRS.

An Updated Review of the Management of Chronic Heart Failure in Patients with Chronic Kidney Disease

“…Since the DIG trial was published, various observational studies have shown increased mortality and hospitalisation rate with patients on digoxin compared to those not on digoxin in patients with HFrEF [ 150 , 151 ]. This is similarly shown in patients with advanced kidney disease [ 152 , 153 ]. The hypothesis regarding the difference in effect is that a prescription bias exists; digoxin is more often prescribed to patients with advanced HF in clinical practice, compared to in a RCT.…”

Demographic trends of cardiorenal and heart failure deaths in the United States, 2011–2020

“…Furthermore, cardiovascular-related mortality makes up nearly half of deaths of people with chronic kidney disease [4]. Overall, co-occurrence of HF and kidney disease leads to an increased risk of mortality [3,[5][6][7][8][9] and may play an important role in therapeutic decision making [10]. The public health burden of these diseases is largely unabated and even increasing in younger adults [11,12].…”