Sacubitril/Valsartan vs Enalapril: Hyperkalemia Risk in HF Patients

For patients with heart failure and reduced ejection fraction who are taking a mineralocorticoid receptor antagonist (MRA), severe hyperkalemia is less common with sacubitril/valsartan treatment than with enalapril, according to new research.

Current guidelines recommend MRAs to reduce morbidity and death for these patients. However, combining MRAs with other inhibitors raise the risk of hyperkalemia.
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To investigate treatment options that may lower the risk of hyperkalemia, the researchers studied 8399 patients with chronic heart failure who had New York Heart Association class II to IV symptoms, had a left ventricular ejection fraction of 40% or less, and were participating in the PARADIGM-HF trial.

They were randomly assigned to either enalapril 10 mg twice daily or sacubitril/valsartan 97/103 mg twice daily in addition to standard treatment.

Hyperkalemia was defined as a potassium level higher than 5.5 mEq/L, and severe hyperkalemia was defined as a level higher than 6.0 mEq/L.

Of the total, 4671 patients were taking an MRA at baseline. They tended to be younger, have a lower ejection fraction, have lower blood pressure, and have more advanced heart failure symptoms than patients not taking an MRA.

After a median 27-month follow-up, the researchers found that severe hyperkalemia was more common among patients taking enalapril than sacubritril/valsartan (3.1 vs 2.2 per 100 patient-years).

Secondary analysis of patients who initiated MRA treatment during the study period showed similar results: 3.3 per 100 patient-years for patients on enalapril vs 2.3 per 100 patient-years for patients on sacubitril/valcartan.

“Among MRA-treated patients with symptomatic [heart failure and reduced ejection fraction], severe hyperkalemia is more likely during treatment with enalapril than with sacubitril/valsartan,” the researchers concluded.

“These data suggest that neprilysin inhibition attenuates the risk of hyperkalemia when MRAs are combined with other inhibitors of the renin-angiotensin-aldosterone system in patients with [heart failure].”

—Amanda Balbi

Reference:

Desai AS, Vardeny O, Claggett B, et al. Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril [published online November 14, 2016]. JAMA Cardiol. doi:10.1001/jamacardio.2016.4733.