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Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System
Andrew P Ambrosy1, Eugene Braunwald2, David A Morrow2
1Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, California; Division of Research, Kaiser Permanente Northern California, Oakland, California.
Insights
Sacubitril/valsartan (S/V) significantly reduced NT-proBNP levels and improved outcomes in acute heart failure patients compared to enalapril. These benefits were consistent regardless of prior heart failure history or ACE inhibitor/ARB use.
Area of Science:
- Cardiology
- Pharmacology
Background:
- The PIONEER-HF trial evaluated sacubitril/valsartan (S/V) in acute decompensated heart failure (HF) patients with reduced ejection fraction.
- Prior HF history and use of ACE inhibitors or ARBs may influence treatment outcomes.
Purpose of the Study:
- To assess the impact of prior HF history and ACE inhibitor/ARB treatment on S/V efficacy in acute decompensated HF patients.
- To compare S/V with enalapril regarding NT-proBNP reduction and clinical outcomes.
Main Methods:
- A prospective, multicenter, double-blind, randomized trial involving 881 patients with ejection fraction ≤40%.
- Patients received in-hospital S/V or enalapril (1:1 randomization).
- Subgroup analyses were conducted based on HF history (de novo vs. chronic) and prior ACE inhibitor/ARB use.
Main Results:
- N-terminal pro-B-type natriuretic peptide (NT-proBNP) significantly declined in all subgroups with S/V showing greater reductions than enalapril.
- No significant interaction was found between prior HF history or ACE inhibitor/ARB treatment and the treatment effect.
- Adverse event rates were similar between S/V and enalapril across all subgroups.
Conclusions:
- Sacubitril/valsartan is safe and effective in stabilized acute decompensated HF patients.
- S/V demonstrated superior NT-proBNP reduction and improved clinical outcomes compared to enalapril.
- Treatment benefits of S/V were consistent irrespective of prior HF history or ACE inhibitor/ARB use.
Background:
The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction.
Objectives:
The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results.
Methods:
The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission.
Results:
At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups.
Conclusions:
Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
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