Background
Some patients with HF may experience a transient decline in eGFR of up to 15-20% after initiation of sacubitril/valsartan [1]. It is unknown whether eGFR decline has an effect on treatment outcome.
Aim of the study
This post hoc analysis of data from the PARADIGM-HF and PARAGON-HF study examined the frequency of eGFR decline after initiation of sacubitril/valsartan, and the extent to which eGFR decline affects the treatment effects of sacubitril/valsartan in HF patients.
Methods
The researchers performed a post hoc analysis of data from the PARADIGM-HF and PARAGON-HF study [2,3]. In these multicenter, double-blind phase 3 studies, patients were randomized between sacubitril/valsartan or enalapril (PARADIGM-HF) or valsartan (PARAGON-HF). In the prematurely terminated PARADIGM-HF study, 8442 patients ≥18 years of age with an LVEF ≤40% and NYHA class II-IV symptoms who additionally had elevated natriuretic peptides levels or had been hospitalized for HF in the past 12 months participated. The PARAGON-HF study enrolled patients ≥50 years of age with symptomatic HF, an LVEF ≥45%, NYHA class II-IV symptoms, elevated natriuretic peptides levels and evidence of structural heart disease. During sequential run-in periods, enalapril was titrated to 10 mg b.d. and then sacubitril/valsartan to 97/103 mg b.d. (PARADIGM-HF), or valsartan was titrated to 80 mg b.d. and then sacubitril/valsartan to 49/51 mg b.d. (PARAGON-HF). eGFR decline was defined as a deterioration in eGFR >15% during the run-in period.
Outcomes
The researchers were interested in: the frequency of eGFR decline after initiation of sacubitril/valsartan; and the extent to which such eGFR decline affects the treatment effects of sacubitril/valsartan on the primary outcome and safety outcomes. The primary outcome was a composite of CV death and first hospitalization for HF (PARADIGM-HF) or total hospitalizations for HF (PARAGON-HF). Safety outcomes were the frequency of hypotension (PARADIGM-HF: SBP<90 mmHg; PARAGON-HF: SBP <100 mmHg), elevated serum creatinine levels (≥2.0, ≥2.5 and ≥3.0 mg/dL), hyperkalemia, and drug discontinuation.
This post hoc analysis of data from the PARADIGM-HF and PARAGON-HF study shows that the treatment effect of sacubitril/valsartan versus a RAS inhibitor on CV and safety outcomes is independent of eGFR decline after initiation of sacubitril/valsartan in patients with HF.
1. Mullens W, Damman K, Testani JM, et al. Evaluation of kidney function throughout the heart failure trajectory - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020;22:584-603.
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