Mineralocorticoid receptor antagonism in Heart Failure

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Mavrakanas TA, Giannetti N, Sapir-Pichhadze R, Alam A: Mineralocorticoid Receptor Antagonists and Renal Outcomes in Heart Failure Patients with and without Chronic Kidney Disease. Cardiorenal Med DOI 10.1159/000503223


After many years of study, the long term outcomes of patients with congestive heart failure (HF), with and without concomitant chronic kidney disease (CKD) treated with mineralocorticoid antagonists (MRA), remains uncertain, especially for patients with HF and preserved ejection fraction (HFpEF).

Mavrakanas and co-workers sought to help resolve (in part) this uncertainty by conducting a retrospective, single center, observational cohort study. Patients with HF, only 9% of whom had HFpEF, treated with renin-angiotensin system (RAS) inhibitor and a MRA (n=314) were compared to those receiving a RAS inhibitor alone (n=1116). The median follow up was 39 months.

Among the RAS inhibitor + MRA cohort 121/314 had CKD (mostly stage 3) and among the RAS inhibitor alone cohort 408/1116 had CKD (again mostly stage 3). MRA had to be discontinued in 93/287 patients, often due to hyperkalemia. Interestingly a doubling of serum creatinine occurred more frequently in those without CKD at baseline, but MRA use seemed to confer a marginal renoprotective effect in those with CKD, perhaps independently of the antihypertensive effect of adding MRA to the regimen. The low rate of CKD progression events rendered the study underpowered to study the true effect on CKD progression. The study was not designed to test differences in efficacy or safety if various MRA available by prescription. Safety issues were reassuring in that adding MRA to RAS inhibitors did not seem to worsen the occurrence of hyperkalemia. Importantly, the beneficial effects of MRA added to RAS inhibition on mortality in patients with HF was lost when the eGFR fell to below 30ml/min/1.73m2. However, due to the low numbers of patients with stages 4 and 5 CKD, the safety of addition of MRA could not be examined.

This well-done cohort study raises more questions than it answers, but it does provide a wealth of data that will be useful for the design of future randomized controlled trials to properly settle the issues concerning the benefits and risks of the use of MRA in patients with HF, with and without concomitant CKD.


Richard Glassock


Quoted Karger Article

Mineralocorticoid Receptor Antagonists and Renal Outcomes in Heart Failure Patients with and without Chronic Kidney Disease