Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie, Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, D - 13353, Berlin, Germany.
Eur J Clin Pharmacol. 2021 Jul;77(7):1029-1037. doi: 10.1007/s00228-020-03066-w. Epub 2021 Jan 26.
Ivabradine has been approved for the treatment of chronic heart failure and chronic stable angina pectoris in Europe. Based on adverse outcomes of reproductive animal studies and the lack of human data, ivabradine is considered contraindicated during pregnancy. The aim of this observational study is to analyse ivabradine use before and during pregnancy.
We evaluated all ivabradine-related requests to the German Embryotox Institute from 2007 to 2019. Exposed pregnancies were analysed as to their outcome.
Off-label use for supraventricular tachycardia was frequent in women of childbearing age. Of 38 prospectively ascertained pregnancies with ivabradine exposure and completed follow-up, 32 resulted in live births, 3 in spontaneous abortions, and 3 were electively terminated. One neonate presented with major birth defects (atrial septal defect and cleft palate). In 33/38 patients, ivabradine was discontinued after confirmation of pregnancy without cardiac deterioration and 5/38 women continued ivabradine throughout pregnancy. In addition, there were 3 retrospectively reported pregnancies including one major birth defect (tracheal atresia).
This case series represents the largest cohort of ivabradine-exposed pregnancies, published so far. According to our findings, ivabradine appears not to be a major teratogen. However, established drugs of choice with strong evidence of low risk for the unborn should be preferred in women planning pregnancy. After inadvertent exposure during pregnancy or lack of treatment alternatives, fetal ultrasound for structural anomalies and growth restriction is recommended. In addition, close monitoring is necessary in pregnant women with supraventricular arrhythmias or cardiac disease.
依伐布雷定已在欧洲获批用于治疗慢性心力衰竭和慢性稳定型心绞痛。基于生殖动物研究的不良结局和缺乏人类数据，依伐布雷定在妊娠期间被认为是禁忌的。本观察性研究旨在分析妊娠前和妊娠期间依伐布雷定的使用情况。
我们评估了德国胚胎毒性研究所 2007 年至 2019 年期间所有与依伐布雷定相关的请求。对有暴露的妊娠进行了结局分析。
在育龄妇女中，依伐布雷定被超适应证用于治疗室上性心动过速。在 38 例前瞻性确定的依伐布雷定暴露并完成随访的妊娠中，32 例分娩活产，3 例自然流产，3 例选择性终止妊娠。1 例新生儿出现重大出生缺陷（房间隔缺损和腭裂）。在 33/38 例患者中，在确认妊娠后，在没有心脏恶化的情况下停用了依伐布雷定，而 5/38 例患者在整个妊娠期间继续使用依伐布雷定。此外，还有 3 例回顾性报告的妊娠，包括 1 例重大出生缺陷（气管闭锁）。
本病例系列是迄今为止发表的最大的依伐布雷定暴露妊娠队列。根据我们的发现，依伐布雷定似乎不是主要的致畸物。然而，在计划妊娠的女性中，应首选具有强有力的低风险证据的已确立的首选药物。如果在妊娠期间意外暴露或缺乏治疗替代方案，建议进行胎儿超声检查以排除结构异常和生长受限。此外，对于患有室上性心律失常或心脏病的孕妇，需要密切监测。
