脑啡肽酶及其抑制剂在心力衰竭治疗中的研究概述

脑啡肽酶(NEP)是一种普遍存在的金属肽酶,可以水解体内多种肽类物质.目前研究证明,NEP可以通过调节利钠肽系统、肾素-血管紧张素-醛固酮系统和激肽-激肽释放酶系统等影响心力衰竭进展,血管紧张素受体脑啡肽酶抑制剂在临床应用的益处也得到证实,因此NEP可以作为治疗心力衰竭的新靶点.然而也正因为NEP作用的广泛性,引发了人...     

血管紧张素受体拮抗剂脑啡肽酶抑制剂对心力衰竭患者肾功能的影响

心力衰竭(心衰)患者常伴随肾功能损害,这不仅严重危害了这类患者的身心健康,还使其治疗复杂化。尽管目前已有众多的抗心衰药物,但心衰患者的病死率和并发症发生率仍居高不下,形势相当严峻。首个血管紧张素受体拮抗剂脑啡肽酶抑制剂(ARNI)的出现给心衰患者带来了新的希望,除了可以有效降低心衰患者死亡和住院风险外,ARNI还可以保护心衰患者的肾功能,甚至对同时合并糖尿病、高血压等疾病的心衰患者的肾功能保护也有效。本文就ARNI对心衰患者肾功能的影响进行阐述。     

血管紧张素受体-脑啡肽酶抑制剂在心力衰竭治疗中的研究进展

心力衰竭治疗策略的变化与其病理生理机制的演变是统一的。现通过对神经内分泌机制中利钠肽系统的介绍增加对血管紧张素受体-脑啡肽酶抑制剂的认识,同时对其目前在随机对照研究及真实世界研究取得的进展进行汇总,最后对血管紧张素受体-脑啡肽酶抑制剂的临床应用提出一些思考,以供临床借鉴。     

心力衰竭新药的临床研究

肾素-血管紧张素-醛固酮系统是治疗心力衰竭的有效靶点,直接肾素受体阻滞剂阿利吉仑,可有效地降低血压,改善左室舒张功能。目前对于左室射血分数保留的心力衰竭(HFpEF)药物治疗的效果不佳,一些新的研究结果表明,血管紧张素受体脑啡肽酶抑制剂LCZ696可能为HFpEF患者的治疗带来希望。左西孟旦、托伐普坦、奈西立肽可以改善急性心力衰竭患者的症状。     

血管紧张素受体脑啡肽酶抑制剂治疗伴射血分数降低的心力衰竭的安全性和有效性观察

目的:观察血管紧张素受体脑啡肽酶抑制剂(ARNI)沙库巴曲/缬沙坦在治疗伴有射血分数降低的心力衰竭(HFrEF)的安全性和有效性。方法:收集2017年12月-2018年11月于我院门诊及住院治疗的左室射血分数(LVEF)≤40%的慢性心力衰竭患者。口服沙库巴曲/缬沙坦治疗的患者设为观察组(沙库巴曲/缬沙坦+指南心力衰竭标准治疗,除外ACEI/ARB,50例);选取年龄、性别及LVEF与观察组相匹配,口服贝那普利(洛汀新)的患者设为对照组(贝那普利+指南心力衰竭标准治疗,57例);随访6～12个月,平均随访202 d。主要比较2组患者的心血管死亡事件发生率、全因死亡率及心力衰竭再住院率;同时比较2组患者的6 min步行试验、BNP及LVEF水平;以及对伴有低血压及严重肾功能不全的慢性心力衰竭患者的安全性及耐受性。结果:结果显示,与贝那普利相比,沙库巴曲/缬沙坦使终点事件相对风险降低了33%(HR=0.67,95%CI:0.46～0.87,P=0.022),其中心血管病死率(HR=0.58,95%CI:0.34～0.74,P=0.031)、因心力衰竭无计划再住院率(HR=0.65,95%C...     

心力衰竭新药的临床研究

肾素-血管紧张素-醛固酮系统是治疗心力衰竭的有效靶点,直接肾素受体阻滞剂阿利吉仑,可有效地降低血压,改善左室舒张功能。目前对于左室射血分数保留的心力衰竭（HFpEF）药物治疗的效果不佳,一些新的研究结果表明,血管紧张素受体脑啡肽酶抑制剂LCZ696可能为HFpEF患者的治疗带来希望。左西孟旦、托伐普坦、奈西立肽可以改善急性心力衰竭患者的症状。     

心力衰竭诊断与药物治疗的研究进展

近年来,心力衰竭(HF)在器械设备治疗方面取得了显著进展,在药物治疗方面直到2019年才取得突破性的进展。其中,多项研究证实血管紧张素Ⅱ受体/脑啡肽酶抑制剂(ARNI)联合制剂——沙库巴曲缬沙坦是治疗HFrEF的有效药物;同时,大量RCT研究数据表明钠-葡萄糖共转运蛋白-2抑制剂(SGLT-2)具有心脏保护作用。尽管在HFpEF方面的研究进展缓慢,但研究显示ARNI和SGLT-2抑制剂有望成为其突破口。此外,2019年ESC对HFpEF的诊断提出了新的算法,有助于其在临床中寻找到有效的治疗方法。本综述对HFrEF和HFpEF在诊断和药物治疗方面的最新进展进行了相关总结,为临床提供参考。     

老年慢性射血分数保留心力衰竭的危险因素分析及其与脑啡肽酶的相关性研究

目的明确老年慢性射血分数保留心力衰竭(HFpEF)的独立危险因素及HFpEF与血清脑啡肽酶(NEP)的关系。方法入选2014年1月至2017年1月在首都医科大学附属北京友谊医院医疗保健中心心血管病房住院的老年慢性HFpEF患者31例。同时选取性别、年龄、患病及用药情况与之相匹配的同期住院的非心力衰竭患者25例作为对照组。通过酶联免疫法测定血清NEP的浓度,比较两组NEP及其他参数的差异。采用SPSS 16.0软件进行数据处理。根据数据类型,分别采用t检验或x~2检验。参数检验采用Pearson相关分析,非参数检验采用Spearman相关分析。建立logistic回归模型,采用逐步向后法分析HFpEF的独立危险因素。结果与对照组相比,HFpEF组的NT-proBNP[(3857.7±618.7)vs(1960.3±331.4)ng/L,P=0.000]、血尿酸[(363.34±147.56)vs(332.11±84.58)μmol/L,P=0.042]、左房内径[(44.29±7.34)vs(37.59±2.97)mm,P=0.007]及左心室舒张末期内径[(54.43±8.41)vs(49.13±2.77)mm,P=0.013]均显著增加,而血清NEP[(0.82±0.33)vs(0.98±0.62)ng/ml,P=0.001]水平显著降低,差异均具有统计学意义(P0.05)。调整混杂变量后,仅NT-proBNP(95%CI:1.000~1.004,P=0.037)是HFpEF的独立预测因子。NEP与NT-proBNP、NYHA分级及超声心动指标均不具有相关性,差异均无统计学意义(P0.05)。结论 NT-proBNP是老年HFpEF的独立危险因素,血清NEP与NT-proBNP无相关性,对老年HFpEF风险的预测价值有限。     

血管紧张素受体脑啡肽酶抑制剂治疗射血分数中间值心力衰竭的疗效分析

目的:探讨血管紧张素受体脑啡肽酶抑制剂治疗射血分数中间值心力衰竭(HFmrEF)患者的有效和安全性.方法:纳入2017年1月至2019年4月,在我院治疗的HFmrEF患者116例,分为ARNI组(给予沙库巴曲缬沙坦钠片,100 mg,2次/d,n=58)和ARB组(给予缬沙坦胶囊,80 mg,1次/d,n=58).比较...     

血管紧张素受体-脑啡肽酶抑制剂治疗射血分数保留型心力衰竭的研究进展

随着目前人口老龄化的加剧,射血分数保留型心力衰竭(HFpEF)在心力衰竭患者中占比日益升高,而传统治疗慢性心力衰竭的药物未能显著改善HFpEF患者的预后。近年来观察到在射血分数降低型心力衰竭(HFrEF)患者中有明确疗效的血管紧张素受体-脑啡肽酶抑制剂(ARNI)被认为有可能改善HFpEF患者的现况。考虑到HFpEF给社会带来的经济负担,及心力衰竭治疗领域需不断创新发展,ARNI在HFpEF患者中的疗效被寄予厚望。然而,全世界与此相关的大型临床研究屈指可数。本综述旨在探讨ARNI的代表药物沙库巴曲缬沙坦在延缓HFpEF进程中可能的作用机制及临床应用进展。     

Angiotensin receptor blocker neprilysin inhibitors

Heart failure (HF) is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with, or eject, blood. It is a multifaceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. Regarding the mechanism of HF, three neurohumoral factors - the renin-angiotensin-aldosterone system, the sympathetic nervous system, and natriuretic peptides — are related to the pathology of chronic HF (CHF), and the targets of treatment. Angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), has been introduced as a treatment for CHF. SAC/VAL is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction (HFrEF), and reduces hospital admissions. An in-hospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL. In the last five years, SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. On the other hand, further work, with carefully designed and controlled preclinical studies, is necessary for understanding the molecular mechanisms, effects, and confirmation of issues such as long-term safety in both human and animal models.     

Angiotensin receptor neprilysin inhibitor as a novel antihypertensive drug: Evidence from Asia and around the globe

Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt‐sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first‐in‐class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin‐sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)‐mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single‐molecule property that may be considered as first‐line antihypertensive therapy. Further investigations are needed to validate its safety for long‐term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.     

The natriuretic peptides in heart failure

Abstract. Synthesis and release of the natriuretic peptides rises incrementally with increasing degrees of cardiac dysfunction. The prime stimulus is intracardiac distending pressures with modulating inuences including age, gender, renal function and other aspects of neurohormonal status. Measurements of plasma natriuretic peptide concentrations and of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide, in particular, show promise in diagnosis of heart failure, risk stratication in those with known heart disease, and in adjustment of therapy. Recombinant B-type natriuretic peptide itself can be administered as a treatment. These diagnostic, prognostic and therapeutic applications of B-type natriuretic peptide require a considerable expansion beyond current evidence, but it appears likely that the true role of plasma peptide measurements and peptide administration will become rmly established within the coming 5 year period.     

Candesartan in heart failure

Candesartan cilexetil is a nonpeptide selective blocker of the angiotensin II receptor sub-type 1. It is a prodrug that is converted to its active metabolite during its variable absorption. It is highly protein bound with a small volume of distribution and a nine-hour half-life. Candesartan is one of two angiotensin receptor blockers approved for use in heart failure. MEDLINE was searched using OVID and PubMed to evaluate the evidence for using candesartan in patients with heart failure. Pharmacologic and pharmacokinetic evaluations, as well as clinical trials, were selected and are presented in this review. Clinical evidence supports the indication for use in systolic heart failure. Results for use in patients with diastolic heart failure were non-significant. Candesartan was well tolerated in the trials, with hyperkalemia, renal dysfunction, and hypotension being the most common adverse events. Use of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors needs further study; however, candesartan appears to provide added benefit in this setting. Candesartan is a safe and effective option for patients with systolic heart failure. Data regarding other angiotensin receptor blockers is underway.     

Critical angioedema induced by a renin angiotensin system blocker in the contemporary era of increasing heart failure: A case report and commentary

Bradykinin‐mediated angioedema, a nonallergic reaction most commonly caused by renin angiotensin system (RAS) blockers, has the potential to lead to a critical condition. RAS blockers are important for treating heart failure and are widely used in clinical settings. We present the case of an 85‐year‐old man who was administered enalapril after percutaneous coronary intervention for an acute myocardial infarction and developed severe angioedema requiring a tracheostomy. He had multiple risks for angioedema including advanced age, smoking history, renal dysfunction, and longstanding use of an angiotensin receptor blocker. The prompt diagnosis of drug‐induced angioedema is critical and depends on physicians'' recognition of risk factors and knowledge of pathophysiology. In the present era of increasingly prevalent heart failure, it is imperative that the possibility of angioedema receives attention, especially given the continuing reliance on RAS blockers and the advent of angiotensin receptor neprilysin inhibitors, a new type of heart failure drug.     

舒张性心力衰竭与收缩性心力衰竭临床特征的比较

目的:探讨舒张性心力衰竭和收缩性心力衰竭患者临床特征的差异。方法:选择心力衰竭患者253例,其中舒张性心力衰竭118例,收缩性心力衰竭135例。登记患者的临床资料,分析各组患者临床特征的差异。所有患者均检测N末端脑钠尿肽前体(NT-proBNP)及高敏C反应蛋白(hs-CRP)。结果:舒张性心力衰竭和收缩性心力衰竭均以老年患者居多,前者以女性多见(56.8%),并发高血压病(81.4%)及心房颤动(26.3%)均高于于后者(前项P0.01,后项P0.05),并发冠心病(45.8%)少于后者(P0.01);两组NT-proBNP及hs-CRP均随着NYHA心功能分级增加而显著升高(P0.01),舒张性心力衰竭组NT-proBNP低于收缩性心力衰竭组(P0.01),但hs-CRP两组间差异无统计学意义。结论:与收缩性心力衰竭相比,舒张性心力衰竭于老年女性更多见,高血压病患病率及心房颤动发生率较高,NT-proBNP水平较低。