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.

中文翻译：

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住院后不久因新诊断（新发）心力衰竭患者急性失代偿性心力衰竭而开始使用沙比特利/缬沙坦：TRANSITION研究的亚组分析。

AIMS Sacubitril /缬沙坦对动态失调的心衰（HF）和射血分数降低（HFrEF）的患者（PARADIGM-HF）以及急性失代偿性HF（ADHF）稳定后（PIONEER-HF和TRANSITION）均显示出疗效和耐受性）。但是，尚缺乏新诊断（从头开始）HFrEF中启动沙奎特利/缬沙坦的数据。在这里，我们评估了从头开始与先前诊断为HFrEF的患者的TRANSTION亚组中ADHF引发沙库普利/缬沙坦的耐受性。方法和结果过渡期将1002例患者随机分组至出院前和服用沙比特利/缬沙坦开始（分析组n = 991，排除误随机后）。在此事后分析中，对沙比特利/缬沙坦的耐受性[达到目标剂量（97/103 mg bid ），在随机分配后10周]，对从头（n = 286）和以前的HFrEF（n = 705）亚组的不良事件（AE）和严重的AE（SAE）进行了比较。在第10周，达到既定剂量的HFrEF患者比从头开始的多（56％比45％；相对危险比1.30，95％置信区间1.12-1.52，P <0.001），并且SAE和永久治疗中止的患者更少。沙必比尔/缬沙坦的启动并不能阻止指导性HF疗法的同时启动和滴定。从头开始的患者与以前的HFrEF相比，N端前B型利尿钠肽和高敏感性肌钙蛋白T下降更快，更大，并且HF率降低和全因住院。结论ADHF后，从头开始在新的HFrEF中进行沙比特利/缬沙坦的一线治疗，以及其他指导性治疗的开始，与既往HFrEF患者相比，这是可行的，并且具有更好的风险获益特征。可以考虑早期接受沙必比尔/缬沙坦干预，以延迟新发HFrEF患者的疾病进展。临床试验注册ClinicalTrials.gov，NCT02661217。