Abstract 17948: Reduced Loop Diuretic Use in Patients Taking Sacubitril/Valsartan Compared With Enalapril: The Paradigm-HF Study
Background: Diuretics are frequently used in patients with heart failure but can lead to neurohormonal activation, electrolyte abnormalities, and worsening renal function.
Hypothesis: We hypothesized that patients treated with sacubitril/valsartan would exhibit reduced diuretic dose requirements compared with enalapril in the PARADIGM-HF study.
Methods: 8399 patients with class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200mg bid or enalapril 10mg bid in the PARADIGM-HF trial. We assessed loop diuretic dose at baseline, 6 months, 1 year and 2 years, calculated furosemide dose equivalents via multiplication factors (4x for torsemide and 40x for bumetanide), and determined changes in loop diuretic dose.
Results: At baseline, 65% of participants were taking loop diuretics with recorded dosage data available (furosemide N=4549, bumetanide N=104, and torsemide N=886). Mean baseline furosemide equivalent doses were 52.3 mg for sacubitril/valsartan and 53.6 mg for enalapril (p=0.33). Loop diuretic use was largely consistent throughout the study, with 73% having no change from baseline at 2 years, but increased dosage (16%) was significantly more likely than decreased dose (11%) overall (p<0.001). Patients treated with sacubitril/valsartan were more like to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post randomization (figure), with a decreased net change in diuretic use of 1.6% (p = 0.05), 3.5% (p < 0.001), and 5.0% (p < 0.001) at 6, 12, and 24 months respectively. Results were similar in an on-treatment analyses.
Conclusions: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics in patients with heart failure with reduced ejection fraction.
Author Disclosures: O. Vardeny: Research Grant; Significant; Novartis. Honoraria; Significant; Novartis. Consultant/Advisory Board; Significant; Novartis. B. Claggett: None. J. Kachadourian: Employment; Significant; Novartis. M. Packer: Consultant/Advisory Board; Significant; Novartis. M. Zile: Research Grant; Significant; Novartis, Amgen. Consultant/Advisory Board; Significant; Novartis. J. Rouleau: Consultant/Advisory Board; Significant; Novartis. K. Swedberg: 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. S.D. Solomon: Research Grant; Significant; Novartis. Consultant/Advisory Board; Significant; Novartis.
- © 2016 by American Heart Association, Inc.