Ivabradine exposures reported to United States poison centers 2015–2023

Ivabradine was approved for use in the United States in 2015 for the management of heart failure. It acts through inhibition of sodium channels found in cardiac myocytes (the “funny” pacemaker current, I_f), which reduces heart rate without significantly affecting inotropy. We queried the National Poison Data System^® for reported ivabradine exposures from April 15, 2015–December 31, 2023. Age was stratified into child (0–5 years), adolescent (6–17 years), adult (18–64 years) and geriatric (65+ years). Other descriptive statistics gathered included patient sex, management site, and medical outcome as coded by America’s Poison Centers^®. There were 240 ivabradine exposures, with 55.0% managed on-site and not transferred to a healthcare facility. The most common reported symptom was bradycardia, reported in 36 patients (15.1%). There were 139 cases that were followed to a known outcome. Within this cohort, 60%, 14%, and 27% of patients suffered no effect, minor effect, or moderate effect, respectively. Exposures in children comprised 18.8% of cases; none required intervention. Intentional self-harm exposures comprised 17.1% of all cases and were more likely to have worse outcomes. Five adult patients received intensive therapy (endotracheal intubation, vasopressors, cardiac pacing, hemodialysis). There were no reported deaths from ivabradine exposure. This study has limitations. First, our data source was limited by being retrospective and incomplete; we could only study the information that was reported to poison centers, and exposures were not confirmed by laboratory testing. It is possible that cases without further follow-up had other treatments and clinical effects not reported here. Finally, reports to poison centers likely underestimate the true number of ivabradine exposures. Adults with unintentional, asymptomatic exposures to ivabradine may be candidates for home monitoring. In ivabradine exposures refractory to medical management, clinicians should consider cardiac pacing or other supportive measures as a temporizing measure.

伊伐布雷定（ivabradine）于2015年获美国批准用于心力衰竭的临床管理。其作用机制为抑制心肌细胞上的钠通道（即“怪异”起搏电流I_f），可在不显著影响心肌收缩力的前提下降低心率。本研究检索了2015年4月15日至2023年12月31日期间国家毒物数据系统（National Poison Data System^®）收录的伊伐布雷定暴露病例报告。将研究对象按年龄分层为儿童（0~5岁）、青少年（6~17岁）、成人（18~64岁）及老年（65岁及以上）人群。收集的其他描述性统计指标包括患者性别、处置场所及美国毒物中心（America’s Poison Centers^®）编码的临床转归。本研究共纳入240例伊伐布雷定暴露病例，其中55.0%的患者在现场完成处置，未转诊至医疗机构。最常见的报告症状为心动过缓，共36例患者出现该症状（占比15.1%）。其中139例病例获得了明确的临床转归随访结果。在该随访队列中，分别有60%、14%及27%的患者未出现不良反应、出现轻度不良反应及中度不良反应。儿童暴露病例占总病例数的18.8%，且无一例需要临床干预。蓄意自伤相关暴露占总病例数的17.1%，此类病例的临床转归更差。5例成人患者接受了强化治疗，包括气管插管、血管加压药治疗、心脏起搏及血液透析。目前尚无伊伐布雷定暴露导致死亡的病例报告。本研究存在一定局限性：首先，数据来源为回顾性且不完整，本研究仅能分析上报至毒物中心的病例信息，且暴露情况未经过实验室检测确认；未获得进一步随访的病例可能接受了其他治疗并出现未被记录的临床转归。此外，上报至毒物中心的病例数可能低估了伊伐布雷定暴露的实际发生数量。对于意外暴露且无临床症状的成人伊伐布雷定暴露患者，可考虑采取居家监测措施。对于经内科治疗无效的伊伐布雷定暴露患者，临床医师可考虑采用心脏起搏或其他支持治疗作为临时干预手段。