Cardiovascular Medicine and Surgery
PIONEER-HF trial: Changing practice in patients hospitalized for heart failure
Renin-angiotensin system (RAS) inhibition forms a pivotal part of guideline-recommended therapy for patients with heart failure with reduced ejection fraction (HFrEF).1 Inhibition of the neutral endopeptidase neprilysin increases levels of several vasoactive peptides that inhibit progression of HF.2 The randomized PARADIGM HF trial compared sacubitril/valsartan (angiotensin receptor neprilysin inhibition, ARNI) to enalapril in 8,434 patients with HFrEF and demonstrated a 20% reduction in the primary outcome of cardiovascular death or HF hospitalization (HR 0.80; CI 0.73– 0.87; P <.001) in patients treated with ARNI; mortality and rehospitalization were decreased significantly, as well.3 Importantly, patients had to be clinically stable and complete a sequential run-in period to be eligible for randomization. On this basis, the 2017 HF guideline update recommended transition from RAS inhibition to ARNI in trial-eligible patients.4
The recent PIONEER-HF trial now provides important evidence to support safety of careful initiation of sacubitril-valsartan for hospitalized patients with and without prior exposure to RAS.5 Hemodynamically stable patients were started on a regimen of sacubitril-valsartan, usually at doses half of those used in PARADIGM-HF. The primary endpoint of a decrease in BNP levels was improved significantly with sacubitril-valsartan (ratio 0.71, CI 0.63–0.81; P<.001), and this translated into a significant decrease in the important patient-centered secondary endpoint of rehospitalization.5 ARNI are underutilized in eligible patients; complexity of outpatient drug initiation may contribute.6
Data from this important trial suggest that clinicians should consider initiation of ARNI during hospitalization for acute heart failure. This could increase the number of patients receiving a guideline-recommended therapy that improves outcomes.
Steven M. Hollenberg, MD, FCCP
Steering Committee Chair
References:
1. Yancy CW et al. 2013 ACCF/ AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147.
2. Vardeny O et al. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663.
3. McMurray JJ, et al. Angiotensin– neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993.
4. Yancy CW, 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.
5. Velasquez EJ, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851. Epub ahead of print.
6. Luo N, et al. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from get with the guidelines-heart failure (GWTG-HF). JACC Heart Fail. 2017; 5:305.