Key result
MRA treatment in heart failure patients without CKD increased the risk of persistent creatinine doubling (HR 4.07; 95% CI 1.41-11.73), whereas this risk was not observed in patients with CKD.
Why the study?
The effect of mineralocorticoid receptor antagonists on chronic kidney disease progression in patients with heart failure with or without preexisting chronic kidney disease had not been adequately studied.
Does MRA treatment added to ACEI/ARB affect renal outcomes and hyperkalemia in heart failure patients with and without CKD?
Cohort (n=1,430)
No
Does MRA treatment added to ACEI/ARB affect renal outcomes and hyperkalemia in heart failure patients with and without CKD?
Effect estimate: HR 4.07 (95% CI 1.41-11.73)
p-value: p=0.009 for interaction
MRA treatment added to ACEI/ARB in heart failure patients appears safe in those with CKD, without increasing the risk of persistent renal decline or serious hyperkalemia compared to those without CKD.
May warrant renal monitoring with MRA in HF without CKD; leaves open differential renal safety by CKD status pending randomized confirmation.
INTRODUCTION: The effect of mineralocorticoid receptor antagonists (MRAs) on chronic kidney disease (CKD) progression in patients with heart failure (HF) and with or without preexisting CKD has not been adequately studied. METHODS: We conducted a retrospective cohort study including consecutive adult patients followed at the HF clinic of a tertiary care center who had already been on an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). Exposure to MRAs was assessed at 6 months from registration. Patients who were never exposed to an MRA were the control group. RESULTS: A total of 314 patients who were prescribed an MRA were compared to 1,116 patients who never received an MRA. Among them, 121 and 408 patients, respectively, had CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2). MRAs had to be discontinued in 36/121 patients with CKD (29.8%) and 57/165 patients without CKD (34.5%) (p = 0.39). MRA treatment was associated with a higher risk for persistent creatinine doubling among patients without CKD (hazard ratio 4.07, 95% confidence interval 1.41-11.73). A numerically lower risk was identified among CKD patients (hazard ratio 0.33, 95% confidence interval 0.04-2.78) (p for interaction = 0.009). The primary safety outcome, a composite of any doubling of serum creatinine or any episode of serious hyperkalemia (K+ >6 mmol/L), occurred more commonly in MRA users compared with nonusers in the subgroup of patients without CKD, but not in CKD patients (p for interaction = 0.02). CONCLUSION: MRA treatment in addition to an ACEI or an ARB could be safely prescribed in HF patients with CKD as it is not associated with persistent renal function decline, acute kidney injury, or serious hyperkalemia, compared with ACEI/ARB monotherapy.
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Mavrakanas et al. (2019) conducted a cohort in Heart failure with and without chronic kidney disease (n=1,430). Mineralocorticoid receptor antagonists (MRAs) vs. No MRA exposure (ACEI/ARB monotherapy) was evaluated on Persistent creatinine doubling (patients without CKD) (HR 4.07, 95% CI 1.41-11.73, p=0.009 for interaction). MRA treatment in heart failure patients without CKD increased the risk of persistent creatinine doubling (HR 4.07; 95% CI 1.41-11.73), whereas this risk was not observed in patients with CKD.
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