Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany.
Drugs. 2023 Sep;83(13):1147-1160. doi: 10.1007/s40265-023-01923-3. Epub 2023 Aug 4.
Cardiac arrhythmias remain a common cause of death and disability. Antiarrhythmic drugs (AADs) and antiarrhythmic agents remain a cornerstone of current cardiac arrhythmia management, despite moderate efficacy and the potential for significant adverse proarrhythmic effects. Due to conceptual, regulatory and financial considerations, the number of novel antiarrhythmic targets and agents in the development pipeline has decreased substantially during the last few decades. However, several promising candidates remain and there are exciting developments in repurposing and reformulating already existing drugs for indications related to cardiac arrhythmias. This review discusses the key conceptual considerations for the development of new antiarrhythmic agents, summarizes new compounds and formulations currently in clinical development for rhythm control of atrial fibrillation, and highlights the potential for drug repurposing. Finally, future directions in AAD development are discussed. Together with an ever-increasing understanding of the molecular mechanisms underlying cardiac arrhythmias, these components support a cautiously optimistic outlook towards improved pharmacological treatment opportunities for patients suffering from cardiac arrhythmias.
心律失常仍然是死亡和残疾的常见原因。尽管抗心律失常药物(AAD)和抗心律失常药物具有中等疗效,并且可能产生严重的致心律失常作用,但它们仍然是当前心律失常管理的基石。由于概念、监管和财务方面的考虑,在过去几十年中,处于开发阶段的新型抗心律失常靶点和药物的数量大大减少。然而,仍有一些有前途的候选药物,并且在将已有药物重新用于治疗与心律失常相关的适应症方面取得了令人兴奋的进展。这篇综述讨论了开发新型抗心律失常药物的关键概念性考虑因素,总结了目前正在临床开发用于心房颤动节律控制的新化合物和制剂,并强调了药物再利用的潜力。最后,讨论了 AAD 开发的未来方向。随着对心律失常潜在分子机制的认识不断加深,这些因素为患有心律失常的患者提供更好的药物治疗机会提供了谨慎乐观的前景。