Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Abstract

BackgroundPerceived risks of hyperkalemia and acute renal insufficiency may limit use of mineralocorticoid receptor antagonist (MRA) therapy in patients with heart failure, especially those with diabetes mellitus or chronic kidney disease.Methods and ResultsUsing clinical registry data linked to Medicare claims, we analyzed patients hospitalized with heart failure between 2005 and 2013 with a history of diabetes mellitus or chronic kidney disease. We stratified patients by MRA use at discharge. We used inverse probability–weighted proportional hazards models to assess associations between MRA therapy and 30‐day, 1‐year, and 3‐year mortality, all‐cause readmission, and readmission for heart failure, hyperkalemia, and acute renal insufficiency. We performed interaction analyses for differential effects on 3‐year outcomes for reduced, borderline, and preserved ejection fraction. Of 16 848 patients, 12.3% received MRA therapy at discharge. Higher serum creatinine was associated with lower odds of MRA use (odds ratio, 0.66; 95% confidence interval, 0.61–0.71); serum potassium was not (odds ratio, 1.00; 95% confidence interval, 0.90–1.11). There was no mortality difference between groups. MRA therapy was associated with greater risks of readmission for hyperkalemia and acute renal insufficiency and lower risks of long‐term all‐cause readmission. Patients on MRA therapy with borderline or preserved ejection fraction had greater risks of readmission for hyperkalemia (P=0.02) and acute renal insufficiency (P<0.001); patients with reduced ejection fraction did not.ConclusionsAmong patients with heart failure and diabetes mellitus or chronic kidney disease, MRA use was associated with lower risk of all‐cause readmission despite greater risk of hyperkalemia and acute renal insufficiency.

Mineralocorticoid Receptor Antagonists in High‐Risk Heart Failure Patients With Diabetes Mellitus and/or Chronic Kidney Disease

“…The evidence available from the prospective randomized trials of MRAs in patients with HFrEF would support the use of a MRA in these high‐risk guideline‐eligible patients13 (inclusion if serum K+ <5.0 mmol/L and estimated glomerular filtration rate >30 mL/min per 1.73 m 2 ). Cooper et al10 also point out that “the benefits of therapy may outweigh the risks in this high–risk population” since there was an overall decrease in the risk of readmissions in patients treated with a MRA. One should, however, closely monitor these high‐risk patients.…”

“…Further information in regard to the efficacy and safety of spironolactone in patients with midrange left ventricular function and HFpEF should be forthcoming from the prospectively randomized open label SPIRRIT‐HFpEF (Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction) (n=3200) in which the primary outcome is cardiovascular mortality 16. In those patients with DM and/or RI, one might consider it prudent to await further data from the SPIRRIT trial16 before considering a MRA in view of the increased risk of RI noted by Cooper et al in these patients 10. However, even in these high‐risk patients there was a decrease in the incidence of readmissions without any increase in mortality, which would favor the use of a MRA.…”

“…However, even in these high‐risk patients there was a decrease in the incidence of readmissions without any increase in mortality, which would favor the use of a MRA. While the decision as to whether or not to administer a MRA to these high‐risk patients with borderline and/or preserved ventricular function remains uncertain, the data by Cooper et al10 are of value in focusing our attention on the need to consider new strategies to reduce the risk of hyperkalemia and RI in these high‐risk patients who are at great risk of dying of HF. The availability of new safe and well‐tolerated potassium‐lowering agents such as patiromer should avoid the risks of hyperkalemia associated with MRA use and potentially could allow the long‐term use of a MRA in these high‐risk patients despite the occurrence of hyperkalemia.…”

“…In the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) study of patients with HFpEF randomized to spironolactone, there was a significant increase in the incidence of doubling of serum creatinine but no increase in the need for renal dialysis 11. It should also be pointed out that the absolute increase in the incidence of hospitalizations for hyperkalemia over 3 years in the analysis by Cooper et al10 was relatively low and that previous studies have suggested that the use of a MRA is associated with a reduction in mortality in comparison to placebo in patients with hyperkalemia, at least up to a serum K+ value of 5.5 mmol/L 12…”

“…This benefit of MRA use was associated with a greater risk of readmissions for hyperkalemia and RI at 1 and 3 years. The increased rate of readmissions for RI was, however, restricted to those with borderline and preserved ejection fractions 10. In the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) study of patients with HFpEF randomized to spironolactone, there was a significant increase in the incidence of doubling of serum creatinine but no increase in the need for renal dialysis 11.…”