Gronda Edoardo, Vanoli Emilio, Iacoviello Massimo
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico di Milano UOC di Nefrologia, Dialisi e Trapianto Renale dell'adulto Dipartimento Di Medicina e Specialità Mediche, Milan, Italy.
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Eur Heart J Suppl. 2020 Nov 18;22(Suppl L):L77-L81. doi: 10.1093/eurheartj/suaa140. eCollection 2020 Nov.
Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril-valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence.
射血分数保留的心力衰竭（HFpEF）是一种临床病症，其特征在于病理生理学异质性大，且缺乏有效的治疗方法，随机对照试验产生的令人失望的结果证明了这一点。沙库巴曲缬沙坦提供了创新的治疗理念，该分子结合了血管紧张素受体阻断剂和中性肽链内切酶抑制剂，这提示了一个假设，即它可能会降低HFpEF患者因心力衰竭住院或死于心血管原因的风险。PARAGON-HF试验（ClinicalTrials.gov编号，NCT01920711）研究了II至IV级HF、射血分数为45%或更高、利钠肽水平升高且有结构性心脏病的HF患者，让他们接受沙库巴曲缬沙坦（目标剂量，每日两次，每次97毫克沙库巴曲与103毫克缬沙坦）或缬沙坦（目标剂量，每日两次，每次160毫克）治疗。该试验在总体研究人群中未达到心血管死亡和心力衰竭住院（HFH）的主要结局。一项亚组分析显示，在研究中左心室射血分数低于中位数57%的受试者中，HFH显著降低。这些数据与之前在HFpEF研究中使用坎地沙坦和螺内酯进行的分析结果一致。这些结果为研究血管紧张素醛固酮和肽酶抑制在目前缺乏有效证据的未探索的HF中等射血分数范围内的疗效打开了大门。
