Université de Lorraine, Inserm Clinical Investigation Center at Institut Lorrain du Coeur et des Vaisseaux, University Hospital of Nancy, Nancy, France.
Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Nat Med. 2024 Sep;30(9):2423-2431. doi: 10.1038/s41591-024-03223-z. Epub 2024 Sep 3.
The intersection of cardiovascular disease, metabolic disorders and chronic kidney disease represents a complex clinical picture challenging healthcare systems worldwide. Metabolic-dysfunction-associated steatotic liver disease (MASLD) often manifests sequentially or concomitantly with these diseases, and may share underlying mechanisms and risk factors. Growing evidence suggests that new therapies could have benefits across these diseases, but trial sponsors and investigators tend to be reluctant to include patients with comorbidities-particularly liver diseases-in clinical trials. In this Perspective, we call for inclusion of patients with MASLD and measurement of liver outcomes in cardio-kidney-metabolic trials, when data suggest mechanistically plausible benefits and liver and cardiovascular safety. We discuss the implications of this new paradigm for clinical trial design and considerations for regulatory approval. Finally, we outline the challenges to implementing such an approach and provide recommendations for future clinical trial conduct.
心血管疾病、代谢紊乱和慢性肾脏病的交集代表了一个复杂的临床图景，给全球的医疗保健系统带来了挑战。代谢功能障碍相关的脂肪性肝病（MASLD）常与这些疾病相继或同时发生，并可能具有共同的潜在机制和危险因素。越来越多的证据表明，新的治疗方法可能对这些疾病都有益，但试验赞助商和研究者往往不愿意将患有合并症的患者——特别是肝脏疾病患者——纳入临床试验中。在本观点文章中，我们呼吁在心脏-肾脏-代谢试验中纳入 MASLD 患者，并测量肝脏结局，当数据提示具有合理的机制获益以及肝脏和心血管安全性时。我们讨论了这一新范例对临床试验设计和监管批准的影响。最后，我们概述了实施这种方法的挑战，并为未来的临床试验提供了建议。
