New drugs in preclinical and early stage clinical development in the treatment of heart failure
New drugs in preclinical and early stage clinical development in the treatment of heart failure
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DOI：
10.1080/13543784.2019.1551357
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发表时间：
2019-01-02
影响因子：
6.1
通讯作者：
Delpon, Eva
中科院分区：
文献类型：
--
作者：
Tamargo, Juan;Caballero, Ricardo;Delpon, Eva
导读：心力衰竭（HF）是一个主要的健康问题，因为它的高患病率、高住院率、高死亡率和巨大的医疗费用。心衰包括一组异质性综合征，具有不同的病理生理、临床表现和治疗反应。基础研究已经确定了涉及心衰发病机制的多个假定治疗靶点，许多有前景的药物正在开发中。涵盖领域：本文综述了目前用于心衰治疗的临床前和临床开发的主要药物。通过搜索MEDLINE和PubMed以及注册（clinicaltrials.gov, clinicaltrialsregister）中的试验来确定药物。Eu, pubmed.gov)。专家意见：尽管在心力衰竭伴射血分数降低的药物治疗方面取得了重大进展，但目前还没有令人信服的治疗显示可以改善伴射血分数保留的心力衰竭患者和急性心力衰竭患者的预后。许多有希望的药物出现在临床前模型和小型ii期试验中，但除了少数例外，它们未能达到更大的充分动力的iii期试验的主要终点。哪些新药将被证明是有价值的仍不确定。改善临床结果，延缓或预防心衰恶化和减少住院率应优先考虑未来的药物开发计划。
Introduction: Heart failure (HF) represents a major health problem because of its high prevalence, high rates of hospitalizations, and mortality and significant healthcare costs. HF comprises a heterogeneous group of syndromes with different pathophysiology, clinical presentations, and response to therapy. Basic research has identified multiple putative therapeutic targets involved in the pathogenesis of HF and many promising drugs are under development. Areas covered: This review summarizes the main drugs currently in preclinical and clinical development for HF treatment. Drugs were identified by search of MEDLINE and PubMed and trials from registries (clinicaltrials.gov, clinicaltrialsregister.eu, pubmed.gov) from 2010. Expert opinion: Despite significant advances in the pharmacological treatment of HF with reduced ejection fraction, no treatment has yet convincingly shown to improve outcomes in patients with HF with preserved ejection fraction and acute HF. Many promising drugs emerged in preclinical models and small phase 2 trials, but with a few exceptions, they fail to meet the primary endpoints in larger adequately powered phase 3 trials. Which new drugs will prove valuable remains uncertain. Improving clinical outcomes, delaying or preventing HF worsening and reducing hospital admissions should be prioritized in future drug development programs.