BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
JACC Heart Fail. 2019 Jun;7(6):457-465. doi: 10.1016/j.jchf.2019.02.015. Epub 2019 May 8.
The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial.
Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy.
We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide.
Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum-related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11).
Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255).
本研究旨在比较 PARADIGM-HF 试验中病因学相关的结局（以及沙库巴曲缬沙坦的作用）。
在发达国家，心力衰竭（HF）的病因随时间而变化，在非西方社会也在不断演变。由于病因不同，结局可能有所不同，治疗效果也可能有所不同。
我们根据 PARADIGM-HF 试验中研究者报告的病因，分析了沙库巴曲缬沙坦的结局和作用。分析的结局为主要复合心血管死亡或 HF 住院，以及各组成部分和任何原因导致的死亡。结局通过包括 N 末端 pro-B 型利钠肽在内的已知预后变量进行了调整。
在 8399 例随机患者中，5036 例（60.0%）具有缺血性病因。在 3363 例（40.0%）非缺血性病因患者中，1595 例（所有患者的 19.0%；非缺血性患者的 47.0%）为特发性扩张型心肌病，968 例（所有患者的 11.5%；非缺血性患者的 28.8%）为高血压病因，800 例（所有患者的 9.5%；非缺血性患者的 23.8%）为其他病因（185 例感染/病毒，158 例酒精性，110 例瓣膜性，66 例糖尿病，30 例药物相关性，14 例围产期相关性，237 例其他病因）。尽管缺血性病因患者的所有结局未经调整的发生率最高，但调整后的危险比（HR）与 2 个主要非缺血性病因类别患者无差异；例如，对于主要结局，与缺血性（HR：1.00）相比，高血压为 0.87（95%置信区间 [CI]：0.75 至 1.02），特发性为 0.92（95% CI：0.82 至 1.04），其他为 1.00（95% CI：0.85 至 1.17）。沙库巴曲缬沙坦优于依那普利的益处在各病因类别中一致（主要结局的交互作用；p=0.11）。
在这项全球试验中，近一半的患者患有射血分数降低的非缺血性 HF，其中特发性和高血压性最常见的病因。各病因类别之间的调整结局相似，沙库巴曲缬沙坦优于依那普利的益处也相似。（LCZ696 与依那普利比较对慢性心力衰竭患者发病率和死亡率的疗效和安全性；NCT01035255）。
