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

Abstract

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.

Fulminant myocarditis-associated expanded dengue syndrome in pregnant woman: a case report

“…Ivabradine is given better tolerance and heart rate control in inappropriate sinus tachycardia than bisoprolol (Martino et al 2021). Ivabradine has been known as teratogenic in some animal studies, and future studies are required to refute other findings by Hoeltzenbein M et al, which have shown a low teratogen risk (Hoeltzenbein et al 2021). Trimetazidine has shown no significant reduction in blood pressure compared to nitrates, with the additional benefit of improved left ventricular systolic performance (Meiszterics et al 2017).…”

Overview of Ivabradine Drug: Use and History

“…20 Ivabradine is also frequently used in treating SVT. 21,22 However, its official use necessitates larger-scale clinical trials with more patients.…”

“…In the case of accidental ivabradine exposure or the absence of other treatment options, the study recommended fetal ultrasound for structural anomalies and growth restriction. 21 After oral administration, ivabradine absorption is nearly complete, with peak plasma levels reached in about 1 hour. Because of the first-pass effect in the gut and liver, it has approximately 40% bioavailability.…”

Arrhythmias in Female Patients: Incidence, Presentation and Management

“…Female representation in the seminal electrophysiological clinical trials was generally low (Figure 2). 115,118,[191][192][193][194][195][196][197][198][199][200] This constitutes a major problem especially in EP because important differences exist between males and females with electrocardiographic and electrophysiological characteristics; incidence and presentation of various arrhythmias; and response to different therapies. These differences make it difficult to generalize overall trial findings to females especially when the number of enrolled females is small.…”