Ivabradine use in pregnant women-treatment indications and pregnancy outcome: an evaluation of the German Embryotox database.
PURPOSE
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.


METHODS
We evaluated all ivabradine-related requests to the German Embryotox Institute from 2007 to 2019. Exposed pregnancies were analysed as to their outcome.


RESULTS
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).


CONCLUSION
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.
['Hoeltzenbein|Maria|M|http://orcid.org/0000-0002-2451-4247', 'Lehmann|Marie-Louise|ML|', 'Beck|Evelin|E|https://orcid.org/0000-0003-1008-8563', 'Dathe|Katarina|K|https://orcid.org/0000-0002-8674-5817', 'Schaefer|Christof|C|https://orcid.org/0000-0001-9001-0525']
D000022:Abortion, Spontaneous D000328:Adult D002317:Cardiovascular Agents D000013:Congenital Abnormalities D005260:Female D006801:Humans D000077550:Ivabradine D011247:Pregnancy D011256:Pregnancy Outcome D012189:Retrospective Studies D013617:Tachycardia, Supraventricular
Ivabradine Pregnancy Tachycardia Drug safety Reproductive age