Heart failure (HF) is a common clinical syndrome associated with significant morbidity and mortality, and there remains a clear need for innovative therapies that can modify disease progression. Sacubitril/valsartan (LCZ696) is a novel complex that combines simultaneous neprilysin inhibition and angiotensin II receptor blockade, that has demonstrated significant cardiovascular death or HF hospitalization reduction in the Prospective Comparison of Angiotensin Receptor/Neprilysin Inhibitor (ARNI) With Angiotensin-Converting Enzyme (ACE) Inhibitors to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial when compared with evidence-based doses of the gold standard ACE inhibitor enalapril. In this comprehensive review, the authors discuss historical trials that have investigated clinical outcomes utilizing variable dosing levels of ACE inhibitors or angiotensin receptor blockers in patients with HF with reduced ejection fraction. A critical analysis of the highlighted studies is proposed in the context of current HF management guidelines and HF clinical practice. In conclusion, based on current evidence, it is unclear whether a maximum recommended enalapril dose would promote improved patient outcomes compared with an intermediate dose. However, no prospective study to date comparing ACE inhibitor doses has documented that higher doses result in significant mortality reduction, although the data suggest that there may be a decrease in HF hospitalizations when compared with lower doses.

中文翻译：

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在PARADIGM-HF试验中，依那普利的剂量是否太低？

心力衰竭（HF）是与显着的发病率和死亡率相关的常见临床综合征，并且仍然明显需要可以改变疾病进程的创新疗法。Sacubitril / valsartan（LCZ696）是一种新型复合物，结合了同时抑制脑啡肽酶和血管紧张素II受体的作用，在血管紧张素受体/脑啡肽酶抑制剂（ARNI）与血管紧张素转化酶（ARNI）的前瞻性比较中已显示出显着的心血管死亡或心衰住院率降低与基于证据的金标准ACE抑制剂依那普利的循证剂量相比，ACETI抑制剂可确定对全球死亡率和心力衰竭发病率的影响（PARADIGM-HF）试验。在这份全面的评论中，作者讨论了历史性试验，这些研究利用射血分数降低的HF患者使用可变剂量的ACE抑制剂或血管紧张素受体阻滞剂水平研究了临床结果。在当前的HF管理指南和HF临床实践的背景下，提出了对重点研究的关键分析。总之，根据目前的证据，目前尚不清楚最大推荐剂量的依那普利与中等剂量相比是否能改善患者的预后。但是，迄今为止，尚无前瞻性研究比较ACE抑制剂的剂量，尽管较高的剂量可降低死亡率，但数据表明与较低剂量相比，HF住院治疗的人数可能会减少。