Initiation of Sacubitril/Valsartan After Acute Decompensation of Chronic Heart Failure: The Sooner, the Better
The recently published analysis of data from the extended open-label follow-up of participants in the PIONEER-HF study clearly pointed out the difference in outcomes and prognosis of patients, which is led by the initiation of the combined drug during hospitalization compared to its initiation shortly after discharge.
Introduction and Objectives
The randomized clinical trial PIONEER-HF provided information on the benefit of early initiation of sacubitril/valsartan in patients after an episode of acutely decompensated chronic heart failure with reduced ejection fraction (ADHF). Initiating the combined drug consisting of an angiotensin receptor and neprilysin inhibitor during hospitalization was well tolerated and led to better outcomes than therapy with enalapril. However, the PIONEER-HF study did not provide a basis for comparing the timing of sacubitril/valsartan initiation - whether its initiation during hospitalization for ADHF is significantly more advantageous than its initiation shortly after discharge.
The aim of the extended follow-up was to compare outcomes in patients with different treatment regimens: some were initiated on sacubitril/valsartan in the hospital during the primary, blinded phase of the study, while others were started on enalapril in the hospital and switched to sacubitril/valsartan after discharge during the subsequent open-label phase.
Methodology and Course
Of the 881 participants in the PIONEER-HF study, 94% (n = 832) continued into the open (unblinded) follow-up. This phase lasted 4 weeks and followed the previous 8-week follow-up of patients who were initiated on sacubitril/valsartan (titrated to 97/103 mg twice daily) or enalapril (titrated to 10 mg twice daily) during hospitalization for ADHF after hemodynamic stabilization. After the 8-week visit, patients in the enalapril-treated group were offered a switch to sacubitril/valsartan, also with a target dose of 97/103 mg twice daily. Treatment was unchanged for those initially treated with the combined drug.
Changes in the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) between weeks 8 and 12 and the incidence of a composite outcome including rehospitalization for heart failure or death from cardiovascular (CV) causes between weeks 0 and 12 were monitored.
Results
In patients who continued taking sacubitril/valsartan, there was a further 17.2% decrease in NT-proBNP levels between weeks 8 and 12 (95% confidence interval [CI] -3.2 to -29.1). A more significant decrease in NT-proBNP levels was observed in those who switched from enalapril to sacubitril/valsartan at week 8 - a difference of -37.4% was noted between the two groups (95% CI -28.1 to -45.6; p < 0.001).
Regarding the risk of rehospitalization for heart failure or CV death during the entire 12-week follow-up, patients who started taking sacubitril/valsartan during hospitalization had a significantly lower risk than those who switched to the combined drug from enalapril at week 8 (hazard ratio [HR] 0.69; 95% CI 0.49-0.97).
Conclusion
Switching from enalapril to sacubitril/valsartan 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with HFrEF and recent hospitalization for acute decompensation. Patients who started sacubitril/valsartan during hospitalization had a lower overall incidence of rehospitalizations and CV deaths.
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Source: DeVore A. D., Braunwald E., Morrow D. A. et al.; PIONEER-HF Investigators. Initiation of angiotensin-neprilysin inhibition after acute decompensated heart failure: secondary analysis of the open-label extension of the PIONEER-HF trial. JAMA Cardiol 2020; 5 (2): 202−207, doi: 10.1001/jamacardio.2019.4665.
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