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

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: http://www.clinicaltrials.gov, NCT02661217.

<p>Impact of Sacubitril/Valsartan on Patient Outcomes in Heart Failure: Evidence to Date</p>

“…31 A subgroup analysis of the TRANSITION study showed that as compared to patients with prior HFrEF, the newly diagnosed HFrEF patients achieved target dose at Week 10 (56% versus 45%; relative risk ratio 1.30, 95% CI 1.12 to 1.52, P<0.001), and fewer had serious adverse effects and permanent treatment discontinuations. 32 These patients also showed greater decreases in N-terminal pro-BNP, lower rates of HF and all-cause re-hospitalisation as compared to patients with previous history of HFrEF. 32 In February 2019, the PIONEER-HF trial (The Comparison of Sacubitril/Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode) provided evidence of a reduction in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration with ARNI therapy compared to enalapril therapy (percent change, −46.7% versus 25.3%; ratio of change with sacubitril/valsartan versus enalapril, 0.71; 95% CI, 0.63 to 0.81; P<0.001) as early as one week into therapy.…”

Angiotensin receptor-neprilysin inhibitor for the treatment of heart failure: a review of recent evidence

“…As expected, the incidences of cardiovascular death and rehospitalization for HF were significantly higher in the prior HFrEF group (p = 0.003); however, this finding may be attributed to the unfavorable baseline characteristics of the patients in the prior HFrEF group. Nevertheless, greater reductions in NT-proBNP and high-sensitivity troponin T levels at weeks 4 and 8 were seen in the de novo than in the prior HFrEF groups, which may also have contributed to the improved clinical outcomes of the de novo HFrEF population [35].…”

“…In the TRANSITION study, 29% of patients were newly diagnosed with HFrEF. Senni et al [35] investigated the differences in characteristics and prognosis between patients with de novo HFrEF and those with prior HFrEF in the TRANSITION population. The patients with de novo HFrEF were younger and had higher diastolic blood pressure, more preserved renal function, fewer comorbidities and milder symptoms compared with those with prior HF.…”

February 2020 at a glance: acute heart failure and cardio‐oncology

“…3,8,9 Sacubitril/valsartan improves outcomes of patients with HF and reduced ejection fraction (HFrEF) 10 and can be safely initiated after haemodynamic stabilization during hospitalization. 11 Senni et al 12 Patients with new-onset HF received a higher target dose and had fewer adverse events and a faster and larger decrease in biomarkers compared with those with prior HFrEF. 12 In a meta-analysis of six randomized controlled studies, including 11 359 patients treated with intravenous serelaxin or placebo within the first 16 h of AHF admission, serelaxin administration was associated with a reduction in 5-day worsening HF, markers of renal dysfunction and all-cause mortality.…”

“…11 Senni et al 12 Patients with new-onset HF received a higher target dose and had fewer adverse events and a faster and larger decrease in biomarkers compared with those with prior HFrEF. 12 In a meta-analysis of six randomized controlled studies, including 11 359 patients treated with intravenous serelaxin or placebo within the first 16 h of AHF admission, serelaxin administration was associated with a reduction in 5-day worsening HF, markers of renal dysfunction and all-cause mortality. 13 Outcomes of patients with takotsubo syndrome differ according to their clinical presentation and treatment.…”