Imamura Teruhiko
Second Department of Medicine, University of Toyama, Japan.
J Atr Fibrillation. 2020 Aug 31;13(2):2362. doi: 10.4022/jafib.2362. eCollection 2020 Aug.
Manufacturer/federal drug administration (FDA) recommends inpatient initiation of dofetilide with the manufacturer providing an initiation algorithm. The outcomes of algorithm deviation have not been reported outside of clinical trials.
We sought to perform a chart review of all the patients admitted for inpatient initiation of dofetilide to report on the incidence of protocol deviations and their implications.
We performed a retrospective review of all patients over a 15-month periodwho were initiated on dofetilide for the very first time or reinitiated on dofetilide after a break of three months or more at our institution. We assessed data about patients who were given dofetilide without adherence to the protocol (i.e. protocol deviation).
A total of 189 patients were included in the study with a median age of 66 ± 9 years. Mean baseline QTc interval was 436 ± 32 msec, and 61% (116/189) were in atrial fibrillation (AF) at the time of dofetilide initiation. In 9% (17/189) of patients, the drug was discontinued due to intolerance or inefficacy. Therapy in 49% (93/189) of patients was noted to deviate from manufacturer recommended protocol with deviations more than once in some patients during the same hospitalization. Baseline QTc exceeding 440 msec(>500msec in conduction abnormalities) was the most frequent deviation (25%; 47/189).Ventricular tachyarrhythmia occurred in 4% (7/189) of patients, did not differ between patients, and occurred with and without protocol deviations (5% vs 2%; p = 0.27).
In our retrospective study, there were frequent deviations from the manufacturer-recommended algorithm guidelines for dofetilideinitation, primarily due to prolonged baseline QTc interval. The impact of these protocol deviations on drug discontinuation was uncertain; however, significant adverse events were higher in the deviation group compared to the group that fully adhered to the protocol. Further multicenter studies are warranted to clarify our findings.
制造商/美国食品药品监督管理局（FDA）建议在住院患者中开始使用多非利特，并由制造商提供起始用药算法。除临床试验外，尚未有关于算法偏差结果的报道。
我们试图对所有因住院开始使用多非利特而入院的患者进行病历审查，以报告方案偏差的发生率及其影响。
我们对15个月期间在我院首次开始使用多非利特或在停药三个月或更长时间后重新开始使用多非利特的所有患者进行了回顾性研究。我们评估了未遵循方案（即方案偏差）使用多非利特的患者的数据。
共有189例患者纳入研究，中位年龄为66±9岁。平均基线QTc间期为436±32毫秒，61%（116/189）的患者在开始使用多非利特时处于心房颤动（AF）状态。9%（17/189）的患者因不耐受或无效而停药。49%（93/189）的患者治疗偏离了制造商推荐的方案，部分患者在同一住院期间出现多次偏差。基线QTc超过440毫秒（传导异常时>500毫秒）是最常见的偏差（25%；47/189）。4%（7/189）的患者发生室性快速心律失常，在患者之间无差异，且在有方案偏差和无方案偏差的情况下均有发生（5%对2%；p=0.27）。
在我们的回顾性研究中，多非利特起始用药频繁偏离制造商推荐的算法指南，主要原因是基线QTc间期延长。这些方案偏差对停药的影响尚不确定；然而，与完全遵循方案的组相比，偏差组的严重不良事件发生率更高。有必要进行进一步的多中心研究以阐明我们的发现。
