Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF. Methods and results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12–1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF. Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk–benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF. Clinical Trial Registration: ClinicalTrials.gov, NCT02661217.

Senni, M., Wachter, R., Witte, K., Straburzynska-Migaj, E., Belohlavek, J., Fonseca, C., et al. (2019). Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. EUROPEAN JOURNAL OF HEART FAILURE, 22(2), 303-312 [10.1002/ejhf.1670].

Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study

Senni M
;
2019

Abstract

Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF. Methods and results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12–1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF. Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk–benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF. Clinical Trial Registration: ClinicalTrials.gov, NCT02661217.
Articolo in rivista - Articolo scientifico
de novo; Heart failure; Sacubitril/valsartan; Safety; Tolerability; TRANSITION;
English
303
312
10
Senni, M., Wachter, R., Witte, K., Straburzynska-Migaj, E., Belohlavek, J., Fonseca, C., et al. (2019). Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed (de novo) heart failure: a subgroup analysis of the TRANSITION study. EUROPEAN JOURNAL OF HEART FAILURE, 22(2), 303-312 [10.1002/ejhf.1670].
Senni, M; Wachter, R; Witte, K; Straburzynska-Migaj, E; Belohlavek, J; Fonseca, C; Mueller, C; Lonn, E; Chakrabarti, A; Bao, W; Noe, A; Schwende, H; Butylin, D; Pascual-Figal, D; Transition, I
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/372773
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