Frederick A. Masoudi, MD, MSPH, FACC, FAHA reviewing Desai AS et al. JAMA Cardiol 2016 Nov 14. Ezekowitz JA. JAMA Cardiol 2016 Nov 14.
A post hoc PARADIGM-HF analysis suggests some benefit, but study limitations make an insufficient case for its preferential use in heart failure patients with reduced ejection fraction taking mineralocorticoid receptor antagonists.
Hyperkalemia is a clinical challenge in patients with heart failure and reduced ejection fraction (HFrEF), because the guideline-recommended regimen includes mineralocorticoid receptor antagonists (MRAs) in addition to renin-angiotensin system inhibitors. In a post hoc analysis of data from the manufacturer-sponsored PARADIGM-HF trial (NEJM JW Cardiol Aug 30 2014; [e-pub] and N Engl J Med 2014 Sep; 371:993), investigators compared the incidence of hyperkalemia in patients with HFrEF treated with sacubitril/valsartan versus enalapril. MRA use was encouraged but at physician discretion.
At baseline, 4671 of 8399 patients were receiving an MRA. Compared with nonrecipients, MRA recipients were younger, had higher potassium levels and more-severe HF symptoms, and were more likely to receive diuretics. In MRA recipients, the risk for severe hyperkalemia (potassium level >6.0 mEq/L) was significantly higher in the enalapril group than in the sacubitril/valsartan group (3.1 vs. 2.2 per 100 patient-years; adjusted hazard ratio, 1.41). The between-group difference in risk for hyperkalemia (potassium level, >5.5 mEq/L) was not statistically significant (10.6 and 9.4 per 100 patient-years). In an analysis accounting for in-trial MRA initiation (791 baseline nonrecipients), the risks for severe hyperkalemia were similar to those in the primary analysis (3.3 and 2.3 per 100 patient-years; adjusted HR, 1.43).
CITATION(S):
Desai AS et al. Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril: A secondary analysis of the PARADIGM-HF trial. JAMA Cardiol 2016 Nov 14; [e-pub].
Ezekowitz JA.Hyperkalemia, sacubitril/valsartan, and mineralocorticoid antagonists in patients with heart failure. JAMA Cardiol 2016 Nov 14; [e-pub].
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