沙库巴曲缬沙坦治疗心血管疾病的研究进展

沙库巴曲缬沙坦是首个血管紧张素受体脑啡肽酶抑制剂,可同时抑制脑啡肽酶和阻断血管紧张素受体。《中国心力衰竭诊断和治疗指南2018》对沙库巴曲缬沙坦作了超越欧洲和美国指南的Ⅰ类推荐。2021年美国食品和药品管理局将沙库巴曲缬沙坦批准用于治疗射血分数正常的心力衰竭患者。大量研究显示沙库巴曲缬沙坦在心力衰竭、心肌梗死、心律失常、高血压、慢性肾脏病和糖尿病患者中均发挥有益作用。本文综述了沙库巴曲缬沙坦治疗心血管疾病及其相关疾病的应用进展。     

心力衰竭药物沙库巴曲缬沙坦的研究进展

心力衰竭是一种严重的心血管疾病,发病率及死亡率均较高。新型心力衰竭药物沙库巴曲缬沙坦是第一个血管紧张素受体脑啡肽酶抑制剂,国内外相关研究已证实其在降低死亡率及住院率方面优于依那普利。现对沙库巴曲缬沙坦的作用机制、临床应用及安全性综述如下。     

沙库巴曲缬沙坦在心血管疾病领域的研究进展

血管紧张素受体脑啡肽酶抑制剂沙库巴曲缬沙坦在治疗心血管疾病方面能够抑制心肌重塑,发挥心脏保护作用。阐述沙库巴曲缬沙坦的作用机制及其在心血管疾病领域的研究进展,以期为心血管疾病特别是心力衰竭的治疗提供参考依据。     

沙库巴曲缬沙坦在心血管疾病中应用研究进展

近年来,多项研究表明沙库巴曲缬沙坦治疗射血分数降低的心力衰竭(HFrEF)效果优于传统药物血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体阻滞剂(ARB)。2019年欧洲心脏病学会专家共识会议报告指出,沙库巴曲缬沙坦可作为新发HFrEF或失代偿性心力衰竭〔左心室射血分数(LVEF)<40%〕住院或门诊患者的起始治疗方案。本文综述沙库巴曲缬沙坦在多种心血管疾病如HFrEF、射血分数中间值的心力衰竭、射血分数保留的心力衰竭、急性失代偿性心力衰竭、急性心肌梗死、高血压、慢性肾脏病、糖尿病、儿童心力衰竭中的研究进展,并分析其安全性和不良反应,同时指出未来研究方向。     

沙库巴曲缬沙坦在心力衰竭治疗中的研究进展

沙库巴曲缬沙坦由抑制脑啡肽酶的沙库巴曲和抑制肾素-血管紧张素-醛固酮系统的缬沙坦组成,是目前治疗射血分数降低的慢性心力衰竭患者的新型药物。与依那普利相比,沙库巴曲缬沙坦不仅可进一步降低心力衰竭住院率、心血管病死亡率和全因死亡风险而且有更好的安全性和耐受性。沙库巴曲缬沙坦获得了欧美指南的一致推荐,值得在中国推广应用,现就沙库巴曲缬沙坦的机制及目前应用的现状做一综述。     

沙库巴曲缬沙坦在心血管病中的应用

正沙库巴曲缬沙坦是目前最新的血管紧张素受体-脑啡肽酶抑制剂(angiotensin receptor-neprilysin inhibitor,ARNI),由血管紧张素受体阻滞剂(angiotensin receptor blocker,ARB)(缬沙坦)和脑啡肽酶抑制剂AHU377(沙库巴曲)构成,通过拮抗血管紧张素受体和增强利钠肽功能发挥作用。2015年美国食品药品监督管理局(food and drug administration,FDA)批准沙库巴曲缬沙坦用于心力衰竭一线治疗,其有望成为心力衰竭治疗的"基石",可能将我们带入一个心力衰竭治疗的新时代~([1-2])。另外有研究显示,沙库巴曲缬沙坦还可用于心肌梗死后状态,对心肌重构、纤维化和肥厚均有一定作用~([3])。目前沙库巴曲缬沙坦用于慢性心力衰竭,尤其是射血分数下降的心力衰竭(heart failure with reduced ejection fraction,HFrEF)相关研究已较多,应用于急性失代偿性心力衰竭(acute decompensated heart failure,ADHF)和高血压方面有部分研究,而应用于其他方面的研究则不多。本文就沙库巴曲缬沙坦应用于除HFrEF外其他心血管病的近期应用现状进行综述。     

PARADIGM-HF研究结果解读

心力衰竭的药物治疗虽然取得很多进展,但慢性心力衰竭患者5年死亡率却与恶性肿瘤相似,寻求新的治疗手段已成必需。沙库巴曲缬沙坦由于其肾素-血管紧张素系统和脑啡肽酶的双重抑制作用而进入人们视野。检验沙库巴曲缬沙坦安全性、有效性的PARADIGM-HF研究显示,沙库巴曲缬沙坦与依那普利相比可进一步降低心血管死亡或心力衰竭住院风险20%,同时其耐受性、安全性也更好。研究人群的代表性、亚组分析与总体获益趋势一致性等特点也保证了该研究的高质量和可推广性。沙库巴曲缬沙坦有望今后惠及更多心力衰竭患者。     

合并低血压的HFrEF患者中沙库巴曲缬沙坦的滴定策略

沙库巴曲缬沙坦作为一种新型的血管紧张素受体脑啡肽酶抑制剂, 已经成为射血分数降低的心力衰竭(HFrEF)患者的一线用药, 同时, 沙库巴曲缬沙坦也具有降压作用, 所以, 目前对于合并低血压的HFrEF(HFrEF-LSBP)患者能否从沙库巴曲缬沙坦中获益存在争议。该文对低血压对沙库巴曲缬沙坦滴定的影响进行综述, 并提出了HFrEF-LSBP患者中滴定沙库巴曲缬沙坦的策略, 为该类患者的治疗提供参考。     

沙库巴曲/缬沙坦治疗心血管疾病的研究进展

沙库巴曲/缬沙坦(LCZ696)是目前最新的血管紧张素受体-脑啡肽酶抑制剂(ARNI),由血管紧张素Ⅱ的1型受体拮抗剂(缬沙坦)和脑啡肽酶抑制剂AHU377(沙库巴曲)构成,通过抑制脑啡肽酶活性和拮抗血管紧张素受体发挥作用。2015年,美国食品和药物管理局批准LCZ696用于心力衰竭一线治疗。大量研究表明,LCZ696对心力衰竭、高血压和心肌梗死后状态等有治疗作用,本文就目前LCZ696在心血管疾病中的研究进展做一综述。     

血管紧张素受体脑啡肽酶抑制剂——沙库巴曲缬沙坦治疗心力衰竭的研究进展

近年来,临床心力衰竭诊断率逐年提高,但心力衰竭患者5年生存率改善效果有限。沙库巴曲缬沙坦作为目前世界上唯一在临床应用的血管紧张素受体脑啡肽酶抑制剂,能有效降低多种原因引起的心力衰竭患者再住院率及心血管死亡风险,目前其已被国内外众多临床指南列为Ⅰ类推荐。本文主要综述了沙库巴曲缬沙坦治疗心力衰竭及心力衰竭合并其他常见疾病的研究进展,以期为临床合理应用该药提供参考。     

沙库巴曲缬沙坦治疗心力衰竭的研究进展

沙库巴曲缬沙坦是全球近年来慢性心力衰竭（HF）治疗领域具有突破性的创新药物,它是一种血管紧张素受体-脑啡肽酶抑制剂,可同时抑制肾素-血管紧张素-醛固酮系统并调节利钠肽系统。已被证实为目前首个也是唯一一个较标准治疗显著改善HF患者预后的药物,较依那普利能够显著改善射血分数,降低HF患者的死亡风险及再入院率,目前已被各国HF治疗指南推荐为慢性HF的一线治疗药物。后续更多研究表明,沙库巴曲缬沙坦还有逆转心脏重构、保护肾功能、降低血糖等作用,临床应用范围更加广泛,是应该大力推广的抗HF药物。本文将对沙库巴曲缬沙坦治疗HF的最新研究进展做一综述。     

沙库巴曲缬沙坦在心肌梗死后心力衰竭中的应用进展

心力衰竭(HF)是急性心肌梗死后的严重并发症,尽管目前治疗手段众多,但病死率仍居高不下。近年来,沙库巴曲缬沙坦的出现为心血管疾病领域的治疗带来突破性进展,作为一种新型血管紧张素受体-脑啡肽酶抑制剂,已被列为治疗慢性HF的一线药物,随着在心肌梗死、高血压、糖尿病和肾脏疾病等方面的研究广泛展开,其更多的临床益处被发现。本文主要探讨沙库巴曲缬沙坦在治疗急性心肌梗死后HF中的应用进展。     

沙库巴曲缬沙坦在低收缩压心力衰竭患者中的临床研究

目的 探究沙库巴曲缬沙坦在低收缩压（90~100） mmHg心力衰竭患者中的耐受剂量、治疗效果和安全性。 方法 选取2018年12月~2019年12月就诊于空军军医大学西京医院心内科的心衰患者116例,患者收缩压（90~100）mmHg,随机分为对照组和试验组。对照组在基础治疗上加用缬沙坦,起始剂量20 mg,1次/d;试验组在基础治疗上加用沙库巴曲缬沙坦,起始剂量25 mg,2次/d;接受过ACEI或ARB治疗的患者需停药36 h进行药物洗脱,两组患者治疗开始后每周电话随访血压情况,密切检测不良反应,治疗6个月后评估相关指标。 结果 治疗6个月后,沙库巴曲缬沙坦显著改善患者NYHA心功能分级、左室射血分数（LVEF）、N末端B型利钠肽原(NT-proBNP)、6分钟步行距离(6MWD)、明尼苏达心衰量表评分（MHFQL）等指标（均P<0.05）,且改善程度优于对照组（均P<0.05）。两组心血管不良事件和药物相关不良事件发生率无统计学差异。 结论 收缩压（90~100）mmHg的心衰患者持续接受沙库巴曲缬沙坦滴定治疗能够显著改善心脏功能和生活质量,且改善程度优于缬沙坦。     

Sacubitril/Valsartan: The Newest Addition to the Toolbox for Guideline-Directed Medical Therapy of Heart Failure

Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril. The rate of all-cause mortality was also significantly reduced. Subsequently, the American College of Cardiology/American Heart Association/Heart Failure Society of America recently updated guideline recommendations for Stage C patients with heart failure with reduced ejection fraction to recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril/valsartan in conjunction with other evidence-based therapies to reduce morbidity and mortality. Several analyses have suggested the cost-effectiveness of this new therapy. To ensure tolerability, initiating the lower dosage form of sacubitril/valsartan is warranted in patients with severe renal impairment, moderate hepatic impairment, and low blood pressure, and close monitoring is warranted in such patients. A 36-hour washout period is recommended when switching patients from an angiotensin-converting enzyme inhibitor to sacubitril/valsartan. Similarly, sacubitril/valsartan is contraindicated in patients receiving concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and those with a history of angioedema.     

沙库巴曲缬沙坦治疗心房颤动合并心力衰竭的研究进展

心力衰竭（心衰）和心房颤动（房颤）是两大高发病率和高死亡率的心血管疾病。这两种疾病常共存，且彼此影响相互促进，加速疾病进展，导致患者脑卒中风险、全因死亡率增加，降低患者生活质量。近年来沙库巴曲缬沙坦在治疗心力衰竭、预防心室重构等领域取得重大进展。临床专家进一步探索了其在治疗心衰合并房颤方面的作用，本文对相关研究进展进行综述。     

Management of heart failure and type 2 diabetes mellitus: Maximizing complementary drug therapy

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and occurs in ~25% of patients with heart failure (HF). Patients with co-morbid HF and T2DM are at elevated risk of adverse outcomes, making optimization of complementary drug therapies essential. While research is ongoing, recent advances in drug therapy, including the introduction of sacubitril/valsartan for HF with reduced ejection fraction and the finding of positive cardiovascular effects of glucose-lowering agents (particularly sodium-glucose co-transporter-2 [SGLT2] inhibitors) have the potential to transform pharmacologic management of co-morbid HF and T2DM. In this review, we provide a comprehensive overview of cardiovascular clinical trials of therapies for HF and diabetes mellitus to date and identify areas requiring further investigation. We also discuss the pathophysiologic overlap of the two diseases and explore the complementary therapeutic effects of HF and T2DM drugs, with a particular focus on sacubitril/valsartan and SGLT2 inhibitors.     

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA

Angiotensin receptor–neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM‐HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM‐HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long‐term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin–angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB.     

Sacubitril/Valsartan: From Clinical Trials to Real-world Experience

Purpose of review

Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan.

Recent findings

In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF. Updated clinical practice guidelines have embraced the use of sacubitril/valsartan in preference to ACE inhibitors or ARBs in selected patients.

Summary

In this review, we highlight the clinical trials that led to these key updates to clinical guidelines, offer practical strategies for patient selection and utilization in clinical practice, and identify important areas of uncertainty that require future research.

     

心力衰竭治疗药物的新变革—沙库巴曲缬沙坦

心力衰竭是一项极其重要的危害人类健康的全球性公共卫生问题,是心血管疾病发生发展的终末阶段,其发病率、再住院率及死亡率在逐年不断的增长,这使得进一步开发更为有效的新型心力衰竭治疗药物迫在眉睫,而具有血管紧张素受体脑啡肽酶抑制剂双重作用机制的沙库巴曲缬沙坦的上市为心衰患者的治疗带来了新的变革。