Physicians' Academy for Cardiovascular Education

ARNI reduces outcomes irrespective of HF history or ACEi/ARB use in HFrEF after ADHF

Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists

Literature - Ambrosy AP, Braunwald E, Morrow DA, et al. - J Am Cardiol Coll 2020; 76:1034–48,

Introduction and methods

Based on the results of the PARADIGM-HF trial, several societies recommend that an ACE inhibitor or ARB should be replaced by sacubitril/valsartan in stable HFrEF patients, with a class I recommendation [1-3]. Patients in PARADGIM-HF were ambulatory patients with chronic HFrEF, and patients with de novo HF or patients who were naïve or previously on a low dose of ACEi or ARB were excluded. The PIONEER-HF trial investigated the safety and the potential role of sacubitril/valsartan vs. enalapril in stabilized HFrEF patients after acute decompensated HF (ADHF) [4-6]. Results of the PIONEER-HF trial demonstrated that in-hospital initiation of sacubitril/valsartan vs. enalapril was safe, well tolerated, reduced NT-proBNP and lowered CV death or rehospitalization for HF.

This subanalysis of the PIONEER-HF trial examined the efficacy and safety of sacubitril/valsartan in subgroups of patients with de novo HF compared to those with worsening chronic HF; and in patients who had received an ACE inhibitor or ARB during admission compared to those who were not treated with an ACEi or ARB.

The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial in HFrEF patients stabilized following admission for ADHF. Patients with EF ≤40% and NT-proBNP ≥1600 pg/mL or BNP ≥400 pg/mL were eligible to participate, between 24 h and 10 days from initial presentation while still in the hospital. Patients were randomized in 1:1 ratio to in-hospital initiation of sacubitril/valsartan or enalapril for 8 weeks. Primary endpoint of the trial was time-averaged proportional change in NT-proBNP from baseline to week 4 and 8. This subanalysis included all 881 patients (879 patients for the subanalysis of prior HF status): 303 patients (34%) had de novo HF and 576 chronic HF (66%); 422 patients (48%) were treated with ACEi/ARB and 459 (52%) were not treated with ACEi/ARB. Of the 576 chronic HF patients, 358 were receiving an ACEi or ARB and 218 were not receiving an ACEi or ARB.

Main results


In patients admitted for ADHF, treatment effect on NT-proBNP and clinical outcomes of sacubitril/valsartan vs. enalapril was similar in subgroups of de novo HF patients and those with worsening chronic HF; and in those who received ACEi/ARB and those who did not receive ACEi/ARB. In addition, in these subgroups of patients sacubitril/valsartan was safe and well tolerated.


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Find this article online at J Am Coll Cardiol

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