Abstract 17374: Reduced Risk of Hyperkalemia in Heart Failure Patients Treated With an MRA and Sacubitril/Valsartan Compared With Enalapril: The PARADIGM-HF Trial
Introduction: Current guidelines recommend treating heart failure and reduced ejection fraction with: a) ACE inhibitors, ARBs or sacubitril/valsartan, b) beta-blockers and c) mineralocorticoid receptor antagonists (MRAs). While sacubitril/valsartan was superior to enalapril irrespective of MRA use in PARADIGM-HF, MRAs increase the risk of hyperkalemia, especially when used in combination with other RAS inhibitors.
Hypothesis: Treatment with sacubitril/valsartan compared with enalapril would result in a decreased risk of hyperkalemia in patients concomitantly treated with MRAs.
Methods: PARADIGM-HF randomized 8399 patients to enalapril 10mg bid or sacubitril/valsartan 200mg bid. Potassium levels were measured at every visit. We assessed the risk of severe hyperkalemia (defined as a potassium > 6.0) in each treatment group in those treated with MRAs at baseline, as well as the subsequent risk of those treated with MRAs following randomization in time-updated models.
Results: Patients taking MRAs at baseline (enalapril arm 57%; sacubitril/valsartan arm 54%) were more likely to develop severe hyperkalemia if receiving enalapril compared with sacubitril/valsartan (Figure; 3.1 vs 2.2 per 100 pt-years, HR 1.37, 95% CI 1.06, 1.76, p = 0.015). In patients in whom MRAs were added during the trial, subsequent hyperkalemia was more common in those assigned to enalapril than to sacubitril/valsartan (3.3 vs. 2.3 per 100 pt-years, HR 1.43, 95% CI 1.13, 1.81, p = 0.003).
Conclusions: Hyperkalemia was more common in patients treated with both MRAs and the ACE-inhibitor enalapril than in those treated with MRAs and sacubitril/valsartan. In conjunction with the increased benefit observed in patients treated with sacubitril/valsartan compared with enalapril in PARADIGM-HF, irrespective of MRA use, these data suggest that MRAs can be used more safely in patients being treated with sacubitril/valsartan than in those being treated with ACE-inhibitors.
Author Disclosures: S. Solomon: Research Grant; Significant; Novartis, Amgen. Consultant/Advisory Board; Modest; Novartis. M. Packer: Consultant/Advisory Board; Significant; Novartis. B. Claggett: None. O. Vardeny: Research Grant; Significant; Novartis. Honoraria; Significant; Novartis. M. Zile: Research Grant; Significant; Novartis. Consultant/Advisory Board; Significant; Novartis. K. Swedberg: Consultant/Advisory Board; Significant; Novartis. J. Rouleau: Consultant/Advisory Board; Significant; Novartis. V. Shi: Employment; Significant; Novartis. M. Lefkowitz: Employment; Significant; Novartis. J. McMurray: Research Grant; Modest; Abbvie, Amgen, Cardiorentis, GSK, Novartis, Pfizer, Roche, Sanofi.
- © 2016 by American Heart Association, Inc.