Clinical Trials of Pharmacological Therapies in Acute Heart Failure Syndromes Lessons Learned and Directions Forward
Clinical Trials of Pharmacological Therapies in Acute Heart Failure Syndromes Lessons Learned and Directions Forward
复制标题
DOI：
10.1161/circheartfailure.109.893222
复制
发表时间：
2010-03-01
影响因子：
9.7
通讯作者：
Gheorghiade, Mihai
中科院分区：
文献类型：
--
作者：
Felker, G. Michael;Pang, Peter S.;Gheorghiade, Mihai
急性心力衰竭综合征（AHFS）的特征是心力衰竭（HF）新发或恶化的体征和/或症状逐渐或快速发作，需要紧急治疗，通常导致住院治疗。1，2 AHFS的社会负担是巨大的，在美国每年有100万人住院，在欧洲也有类似的相对数字。2-6持续的流行病学趋势，如人口老龄化、心肌梗死后生存率提高以及除颤器治疗导致的猝死减少，表明导致住院治疗的慢性HF患病率在未来几十年将继续增加。7 AHFS住院后的预后仍然很差，6个月时死亡率或复发住院率接近50%，8-10尽管近年来慢性HF的管理有所改善，但这些结果几乎没有改变。[11]在这些经常被引用的统计数据中隐藏着一个值得注意的矛盾-AHFS的体征和症状（呼吸困难、水肿等）在大多数患者中得到了成功治疗，但出院后的结果仍然令人沮丧，并且尝试开发新的AHFS短期治疗方法在很大程度上是不成功的。自从我们在2005年首次发表以来，14个大型的国际III期开发项目--替佐生坦、12左西孟旦、13托伐普坦、14和rolofylline 15--未能令人信服地证明这些药物在AHFS中的安全性和有效性。即使是被批准用于AHFS治疗的药物（美国的米力农和奈西立肽以及欧洲部分地区的左西孟旦），也一直存在安全性问题。[16-18]从广义上讲，治疗AHF的药物组合--袢利尿剂、血管扩张剂和正性肌力药--与20世纪70年代相比基本没有变化。19.尽管在过去十年中为开发改进的AHFS疗法所做的大量努力取得了令人失望的结果，但我们相信，作为一个科学界，我们现在有更好的条件进行未来的研究。在美国和欧洲的指南中，AHFS的住院治疗现在被认为是一个关键的临床问题。2，6本共识文件产生
Acute heart failure syndromes (AHFS) are characterized by a gradual or rapid onset of new or worsening signs and/or symptoms of heart failure (HF) requiring urgent therapy, usually resulting in hospitalization. 1, 2 The societal burden of AHFS is substantial, with 1 million hospitalizations annually in the United States and similar relative numbers in Europe. 2–6 Ongoing epidemiological trends, such as the aging population, improved survival after myocardial infarction, and a decrease in sudden death due to defibrillator therapy, suggest that the prevalence of chronic HF resulting in hospitalization will continue to increase during the coming decades. 7 The prognosis after hospitalization for AHFS remains bleak, with rates of death or recurrent hospitalization at 6 months approaching 50%, 8–10 outcomes that have changed little in recent years despite improvements in the management of chronic HF. 11 Hidden within these oft-cited statistics is a notable paradox—signs and symptoms of AHFS (dyspnea, edema, etc) are successfully treated in the majority of patients, but postdischarge outcomes remain dismal, and attempts to develop new short-term therapies for AHFS have largely been unsuccessful. Since our initial publication in 2005, 1 4 large, international phase III development programs—tezosentan, 12 levosimendan, 13 tolvaptan, 14 and rolofylline15—have failed to convincingly demonstrate the safety and efficacy of these agents in AHFS. Even for drugs approved for AHFS treatment (milrinone and nesiritide in the United States and levosimendan in parts of Europe), there have been persistent concerns about safety. 16–18 Broadly speaking, the pharmacological armamentarium for AHFS—loop diuretics, vasodilators, and inotropes—is largely unchanged from the 1970s. 19 Although substantial efforts in the last decade to develop improved AHFS therapies have yielded disappointing results, we believe that as a scientific community, we are now better equipped to conduct future studies. Hospitalization for AHFS is now recognized as a critical clinical problem in both the US and European guidelines. 2, 6 This consensus document arose