menu

ReachMD

Be part of the knowledge.
Register

We’re glad to see you’re enjoying ReachMD…
but how about a more personalized experience?

Register for free

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

onlinejacc.org
Literature - Ambrosy AP, Braunwald E, Morrow DA, et al. - J Am Cardiol Coll 2020; 76:1034–48, doi.org/10.1016/j.jacc.2020.06.073

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

  • Patients who received sacubitril/valsartan had a significantly greater decrease in NT-proBNP compared to those who received enalapril, evident at week 1 till week 8 in patients with de novo HF and worsening chronic HF (Pinteraction=non-significant).
  • In patients with worsening chronic HF, there was no difference in treatment effect by sacubitril/valsartan in those who had received an ACEi/ARB compared to those who had not received an ACEi or ARB (Pinteraction=non-significant). Similar findings were observed when all patients were included (de novo HF and worsening HF).
  • Patients assigned to sacubitril/valsartan had a significantly lower incidence of the composite of CV death or rehospitalization for HF in patients with de novo HF and with worsening chronic HF (Pinteraction=non-significant).
  • In patients with worsening HF, sacubitril/valsartan significantly lowered the composite of CV death or rehospitalization for HF compared to enalapril in those on ACEi/ARB, but not in those who did not receive ACEi/ARB. Outcomes were numerically lower though with sacubitril/valsartan vs. enalapril irrespective of ACEi/ARB treatment status. Findings were directionally similar when both patients groups (de novo and worsening chronic HF) were included.
  • Incidence of adverse events, including worsening renal function, hyperkalemia, symptomatic hypotension, angioedema were similar with sacubitril/valsartan vs. enalapril in all 4 subgroups (Pinteraction=non-significant).

Conclusion

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.

References

1. Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: an update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart

Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.

J Am Coll Cardiol 2016;68:1476–88.

2. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the

Heart Failure Society of America. J Am Coll Cardiol 2017;70:776–803.

3. Yancy CW, Januzzi JL Jr., Allen LA, et al. 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With

Reduced Ejection Fraction: a report of the American College of Cardiology Task Force on Expert

Consensus Decision Pathways. J Am Coll Cardiol 2018;71:201–30.

4. Velazquez EJ, Morrow DA, DeVore AD, et al. Rationale and design of the comParIson Of sacubitril/ valsartaN versus Enalapril on Effect on ntpRo- bnp in patients stabilized from an acute

Heart Failure episode (PIONEER-HF) trial. Am Heart J 2018;198:145–51.

5. Velazquez EJ, Morrow DA, DeVore AD, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med 2019;380:

539–48.

6. Morrow DA, Velazquez EJ, DeVore AD, et al. Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF trial. Circulation 2019;139:2285–8.

Find this article online at J Am Coll Cardiol

Facebook Comments

Schedule17 May 2024