Jpn Circ J. 1998 Sep;62(9):633-48. doi: 10.1253/jcj.62.633.
The past fifty years of antiarrhythmic drug development have seen limited success in prolonging life and reducing morbidity. It is likely that arrhythmias are in most instances final common pathways through which changes in the cardiac substrate and in trigger mechanisms are expressed. We propose that the development and administration of therapies for the arrhythmias themselves, while offering a panacea for a disease entity that has evolved and is being overtly manifested, is also an admission of failure to identify and prevent evolution of the substrate and triggers such that arrhythmias can occur. We suggest that while strategies for treatment and prevention of recurrence of arrhythmias still warrant exploration, greater hope for the future lies in identifying means for earlier diagnosis of the arrhythmogenic substrate and triggers, and in developing therapies that are "upstream" to the arrhythmia and prevent their initial expression. Means to achieve this end are suggested, using specific arrhythmias as examples. Similarly, to increase the likelihood that clinical studies of new therapies can be successfully concluded and interpreted, we suggest new approaches to patient selection, risk stratification, trial endpoints, outcome events and trial methodologies.
在过去五十年的抗心律失常药物研发过程中，在延长寿命和降低发病率方面取得的成功有限。在大多数情况下，心律失常可能是心脏基质和触发机制变化得以体现的最终共同途径。我们认为，针对心律失常本身开发和应用治疗方法，虽然为一种已经演变且正在明显表现出来的疾病实体提供了万灵药，但同时也意味着未能识别和预防基质及触发因素的演变，从而导致心律失常发生，这是一种失败的表现。我们建议，虽然治疗和预防心律失常复发的策略仍值得探索，但未来更大的希望在于找到更早诊断致心律失常基质和触发因素的方法，并开发出在心律失常之前发挥作用并防止其最初表现的治疗方法。本文以特定心律失常为例，提出了实现这一目标的方法。同样，为了提高新治疗方法的临床研究能够成功完成并得到合理解释的可能性，我们建议在患者选择、风险分层、试验终点、结局事件和试验方法等方面采用新的方法。
