Di Tano Giuseppe, Di Lenarda Andrea, Gabrielli Domenico, Aspromonte Nadia, De Maria Renata, Frigerio Maria, Iacoviello Massimo, Mortara Andrea, Murrone Adriano, Nardi Federico, Oliva Fabrizio, Pontremoli Roberto, Scherillo Marino, Senni Michele, Urbinati Stefano, Gulizia Michele Massimo
U.O. Cardiologia, Ospedale ASST, Cremona.
S.C. Centro Cardiovascolare, Azienda Sanitaria Universitaria Integrata, Trieste.
G Ital Cardiol (Rome). 2018 Oct;19(10):568-590. doi: 10.1714/2978.29843.
Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction (HFrEF) since the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin-aldosterone system activation through blockade of angiotensin II type 1 receptors and enhances the activity of vasoactive peptides including natriuretic peptides, through inhibition of neprilysin, the enzyme responsible for their degradation. In the landmark PARADIGM-HF trial, patients with HFrEF treated with sacubitril/valsartan had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, a 20% lower risk of cardiovascular death, a 21% to 20% lower risk of a first heart failure hospitalization, and a 16% to 20% lower risk of death from any cause, compared with subjects allocated to enalapril (all p<0.001).Following the trial, new international guidelines endorsed sacubitril/valsartan as a class I recommendation for the management of patients with HFrEF who remain symptomatic despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed by the National Health Service since March 2017 within criteria set by the Italian Medicines Agency subject to patient inclusion in a dedicated monitoring registry. Although numerous post-hoc analyses of the original trial suggested that the benefits of this innovative medication may extend across a variety of subgroups, many questions do not yet have an evidence-based answer.In this position paper, we discuss the current role of sacubitril/valsartan in the management of chronic HFrEF, treatment eligibility and the modulating role of patients' characteristics. Moreover, we address concerns elicited by the PARADIGM-HF study and shortcomings of this novel drug, to clarify the place of this new therapy in the context of global care of heart failure in Italy. Our aim is to provide clinical cardiologists with a concise and practical guidance on when and how to use sacubitril/valsartan, to assist clinicians in closing the gap between scientific innovation and real-world experience.
沙库巴曲缬沙坦，作为首个血管紧张素受体脑啡肽酶抑制剂（ARNI），是自21世纪初以来首个在射血分数降低的慢性心力衰竭（HFrEF）患者中显示出死亡率获益的药物。沙库巴曲缬沙坦通过阻断1型血管紧张素II受体同时抑制肾素-血管紧张素-醛固酮系统激活，并通过抑制负责降解利钠肽等血管活性肽的酶——脑啡肽酶，增强这些肽的活性。在具有里程碑意义的PARADIGM-HF试验中，与接受依那普利治疗的受试者相比，接受沙库巴曲缬沙坦治疗的HFrEF患者的主要复合终点（心血管死亡或心力衰竭住院）降低了20%，心血管死亡风险降低了20%，首次心力衰竭住院风险降低了21%至20%，任何原因导致的死亡风险降低了16%至20%（所有p<0.001）。该试验之后，新的国际指南认可沙库巴曲缬沙坦作为I类推荐用于治疗尽管接受了最佳药物治疗仍有症状的HFrEF患者。在意大利，自2017年3月起，在意大利药品管理局设定的标准范围内，沙库巴曲缬沙坦可由国家卫生服务机构报销，但患者需纳入专门的监测登记系统。尽管对原始试验的众多事后分析表明，这种创新药物的益处可能扩展到各种亚组，但许多问题尚无基于证据的答案。在本立场文件中，我们讨论了沙库巴曲缬沙坦在慢性HFrEF管理中的当前作用、治疗资格以及患者特征的调节作用。此外，我们阐述了PARADIGM-HF研究引发的担忧以及这种新药的缺点，以阐明这种新疗法在意大利心力衰竭全球治疗背景下的地位。我们的目的是为临床心脏病学家提供关于何时以及如何使用沙库巴曲缬沙坦的简洁实用指导，以帮助临床医生缩小科学创新与实际临床经验之间的差距。
