Pharmacology of heart failure: From basic science to novel therapies.
Pharmacology of heart failure: From basic science to novel therapies.
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DOI：
10.1016/j.pharmthera.2016.07.004
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发表时间：
2016-10
影响因子：
13.5
通讯作者：
A. Lother;L. Hein
中科院分区：
文献类型：
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作者：
A. Lother;L. Hein
慢性心力衰竭是美国和欧洲住院治疗的主要原因之一，并伴有高死亡率。目前慢性心力衰竭伴射血分数降低的药物治疗主要基于抑制肾上腺素能和肾素-血管紧张素-醛固酮系统对心脏的有害作用的化合物。在使用安内酯十多年后，最近发布的心力衰竭治疗指南中增加了两种新的治疗原则：hn通道抑制剂伊伐布雷定和血管紧张素和奈普利素抑制剂缬沙坦/苏比利联合使用。处于II期或III期临床评估的新化合物包括新型非甾体矿皮质激素受体拮抗剂、鸟苷酸环化酶激活剂或肌氨酸激活剂。各种新的候选靶点已经被确定，基因转移的可用性刚刚开始加速从基础科学到临床应用的转化。本文从三个阶段综述了目前慢性心力衰竭的药理学和药物治疗：美国心脏协会和欧洲心脏病学会的最新临床指南，临床开发的新药，以及临床前研究中出现的治疗心力衰竭的创新药物靶点及其机制。
Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin–angiotensin–aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril. New compounds that are in phase II or III clinical evaluation include novel non-steroidal mineralocorticoid receptor antagonists, guanylate cyclase activators or myosine activators. A variety of novel candidate targets have been identified and the availability of gene transfer has just begun to accelerate translation from basic science to clinical application.This review provides an overview of current pharmacology and pharmacotherapy in chronic heart failure at three stages: the updated clinical guidelines of the American Heart Association and the European Society of Cardiology, new drugs which are in clinical development, and finally innovative drug targets and their mechanisms in heart failure which are emerging from preclinical studies will be discussed.