Mineralocorticoid receptor antagonist (MRA) therapy is associated with a lower risk of all-cause hospitalization in high-risk patients with heart failure and concomitant diabetes mellitus or chronic kidney disease (CKD), but the medications also increase patients’ risk of hospitalization with hyperkalemia or acute renal insufficiency, according to a new study.

Using clinical registry data linked to Medicare claims, Lauren B. Cooper, MD, of Inova Heart & Vascular Institute, Inova Fairfax Hospital, Falls Church, Virginia, and colleagues studied 16,848 patients hospitalized with heart failure from 2005 and 2013 and who had a history of diabetes mellitus or CKD. Of these, 2067 (12.3%) received MRA therapy at discharge. A significantly higher proportion of the MRA group than the no-MRA group had diabetes mellitus (86.6% vs 82.2%), whereas CKD was significantly less common in the MRA group (27.8% vs 36%). Higher serum creatinine was associated with 34% lower odds of MRA use, but serum potassium level was not associated with MRA use.

The 1- and 3-year all-cause hospital readmission rates were significantly lower for the MRA than no-MRA group. The rates were 68.2% and 84.9%, respectively, for the MRA recipients compared with 72.2% and 88.2%, respectively, for the no-MRA group, Dr Cooper’s team reported online ahead of print in the Journal of the American Heart Association. After inverse probability weighting, MRA use was associated with an 8% and 7% lower risk of readmission at 1 and 3 years, respectively. MRA use was not associated with 30-day, 1-year, or 3-year mortality or 30-day all-cause readmission.


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In weighted analyses, MRA use was associated with a significant 2-fold increased risk of readmission for hyperkalemia at 30 days and 42% and 28% increased risk at 1 and 3 years, respectively. In addition, MRA use was associated with a significant 31%, 17%, and 14% increased risk of 30-day, 1-year, and 3-year readmission with a diagnosis of acute renal insufficiency, respectively.

MRA use was associated with a significant 2.7-fold and 2.2-fold increased risk of readmission with a primary diagnosis of hyperkalemia at 1 and 3 years, respectively. Further, MRA use was associated with a significant 65%, 32%, and 18% increased risk of readmission with a primary diagnosis of acute renal insufficiency at 30 days and 1 and 3 years, respectively.

“Because of the overall decrease in the risk of hospitalization for patients treated with mineralocorticoid receptor antagonist therapy, the benefits of therapy may outweigh the risks in a high-risk population,” the investigators wrote.

Patients receiving MRA therapy with borderline or preserved ejection fraction (HFpEF) had increased risks of readmission for hyperkalemia and acute renal insufficiency, Dr Cooper and her colleagues reported.

“MRAs may be safe in a selected group of patients with heart failure and concomitant diabetes mellitus or renal insufficiency,” the authors concluded.

The investigators pointed out a number of study limitations. “As in all observational studies,” they noted, “unmeasured confounders may have influenced the results.” In addition, because the study population was limited to Medicare fee-for-service beneficiaries, results may not be generalizable to other populations. The researchers also noted that their study patients were recently discharged from an acute heart failure hospitalization. Consequently, their results may not apply to stable outpatients with heart failure, they stated.

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Reference

Cooper LB, Lippman SJ, Greiner MA, et al. Use of mineralocorticoid receptor antagonists in patients with heart failure and comorbid diabetes mellitus or chronic kidney disease. J Am Heart Assoc. 2017; published online ahead of print.