Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Heart Center, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
Pharmacol Ther. 2016 Oct;166:136-49. doi: 10.1016/j.pharmthera.2016.07.004. Epub 2016 Jul 25.
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.
慢性心力衰竭是美国和欧洲住院的主要原因之一，伴有高死亡率。目前，射血分数降低的慢性心力衰竭的药理学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。在螺内酯问世十多年后，两种新的治疗原则最近被添加到心力衰竭治疗指南中：HCN 通道抑制剂伊伐布雷定和血管紧张素和 Neprilysin 抑制剂缬沙坦/沙库巴曲。正在进行 II 期或 III 期临床评估的新化合物包括新型非甾体类盐皮质激素受体拮抗剂、鸟苷酸环化酶激活剂或肌球蛋白激活剂。已经确定了多种新型候选靶点，并且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。这篇综述概述了慢性心力衰竭的当前药理学和药物治疗在三个阶段：美国心脏协会和欧洲心脏病学会的更新临床指南，处于临床开发中的新药，最后是从临床前研究中出现的心力衰竭的创新药物靶点及其机制。
