Despite numerous promising therapeutic targets, there are no proven medical treatments for calcific aortic stenosis (AS). Multiple stakeholders need to come together and several scientific, operational, and trial design challenges must be addressed to capitalize on the recent and emerging mechanistic insights into this prevalent heart valve disease. This review briefly discusses the pathobiology and most promising pharmacologic targets, screening, diagnosis and progression of AS, identification of subgroups that should be targeted in clinical trials, and the need to elicit the patient voice earlier rather than later in clinical trial design and implementation. Potential trial end points and tools for assessment and approaches to implementation and design of clinical trials are reviewed. The efficiencies and advantages offered by a clinical trial network and platform trial approach are highlighted. The objective is to provide practical guidance that will facilitate a series of trials to identify effective medical therapies for AS resulting in expansion of therapeutic options to complement mechanical solutions for late-stage disease.

尽管有许多有希望的治疗靶点，但钙化性主动脉瓣狭窄 (AS) 尚无经过验证的医学治疗方法。多个利益相关者需要聚集在一起，并且必须解决几个科学、操作和试验设计挑战，以利用对这种流行的心脏瓣膜疾病的最近和新兴的机制见解。本综述简要讨论了 AS 的病理生物学和最有希望的药理学靶点、筛查、诊断和进展，临床试验中应针对的亚组的识别，以及在临床试验设计和实施中更早而不是更晚地征求患者意见的必要性。审查了潜在的试验终点和评估工具以及临床试验的实施和设计方法。强调了临床试验网络和平台试验方法提供的效率和优势。目的是提供实用指导，以促进一系列试验，以确定 AS 的有效药物疗法，从而扩大治疗选择，以补充晚期疾病的机械解决方案。