Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359 Bremen, Germany.
Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Achterstraße 30, 28359 Bremen, Germany.
Reprod Toxicol. 2023 Aug;119:108415. doi: 10.1016/j.reprotox.2023.108415. Epub 2023 May 26.
Use of endothelin receptor antagonists (ERAs) and riociguat, approved for treatment of pulmonary hypertension (PH), is contraindicated during pregnancy due to reported teratogenicity in animals. We aimed to investigate prescribing of these drugs in girls/women of childbearing age and to explore - as a secondary aim - the occurrence of pregnancies exposed to these drugs. Using the German Pharmacoepidemiological Research Database (GePaRD, claims data from 20% of the German population) we conducted cross-sectional analyses to determine prescribing prevalence of ERAs and riociguat between 2004 and 2019 and to characterize users and prescribing patterns. In a cohort analysis, we assessed the occurrence of pregnancies exposed to these drugs in the critical time window. Overall, we identified 407 women with ≥ 1 dispensation of bosentan between 2004 and 2019; the respective number was 73 for ambrisentan, 182 for macitentan, 31 for sitaxentan, and 63 for riociguat. In nearly all years, more than 50% of the girls/women were ≤ 40 years. Age-standardized prevalence was highest for bosentan (0.04/1000) in 2012 and 2013, followed by macitentan (0.03/1000) in 2018 and 2019. We observed 10 exposed pregnancies: 5 to bosentan, 3 to ambrisentan, and 2 to macitentan. The increased prevalence of macitentan and riociguat from 2014 onwards might reflect changes in PH treatment. Even though PH is a rare disease and pregnancy should be avoided in women with PH, particularly if they use ERAs, we identified pregnancies exposed to ERAs. Multi-database studies will be needed to assess the risk of these drugs on the unborn child.
内皮素受体拮抗剂 (ERAs) 和 riociguat 被批准用于治疗肺动脉高压 (PH)，由于在动物中报告有致畸性，因此在怀孕期间禁用。我们旨在研究这些药物在育龄女孩/妇女中的使用情况，并作为次要目标，探讨暴露于这些药物的妊娠情况。我们使用德国 Pharmacoepidemiological Research Database (GePaRD，来自 20%德国人口的索赔数据) 进行了横断面分析，以确定 2004 年至 2019 年期间 ERA 和 riociguat 的处方流行率，并描述使用者和处方模式。在队列分析中，我们评估了在关键时间窗口暴露于这些药物的妊娠发生情况。总体而言，我们确定了 407 名在 2004 年至 2019 年期间至少有 1 次波生坦配药的女性；安贝生坦的相应数量为 73，马西替坦为 182，西他生坦为 31， riociguat 为 63。在几乎所有年份，超过 50%的女孩/妇女年龄在 40 岁以下。2012 年和 2013 年，波生坦的年龄标准化患病率最高 (0.04/1000)，其次是马西替坦 (0.03/1000)，2018 年和 2019 年。我们观察到 10 例暴露于妊娠的病例：5 例使用波生坦，3 例使用安贝生坦，2 例使用马西替坦。从 2014 年开始，马西替坦和 riociguat 的患病率增加，这可能反映了 PH 治疗的变化。尽管 PH 是一种罕见疾病，并且应避免患有 PH 的妇女怀孕，特别是如果她们使用 ERAs，则我们发现了暴露于 ERAs 的妊娠。需要多数据库研究来评估这些药物对未出生婴儿的风险。
