Abstract：
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.
摘要：
使用内皮素受体拮抗剂（ERAs）和利奥西瓜，批准用于治疗肺动脉高压（PH），由于报告的动物致畸性，在怀孕期间是禁忌的。我们的目的是调查这些药物在育龄妇女/女孩中的处方，并探讨暴露于这些药物的怀孕的发生作为次要目标。使用德国药物流行病学研究数据库(GePaRD，来自20％德国人口的索赔数据）我们进行了横断面分析，以确定2004年至2019年期间ERA和riociguat的处方患病率，并描述用户和处方模式。在队列分析中，我们在关键时间窗内评估了暴露于这些药物的妊娠发生情况.总的来说,我们在2004年至2019年间确定了407名服用波生坦≥1次的女性；abrisentan的人数分别为73，182用于Macitentan，31代表西塔克森坦，63分给里奥西加特。在几乎所有的岁月里,超过50%的女孩/妇女年龄≤40岁。2012年和2013年，波生坦的年龄标准化患病率最高（0.04/1,000），2018年和2019年其次是马西坦（0.03/1,000）。我们观察到10次暴露怀孕：波生坦5次，3给ambrisentan，和2到Macitentan。从2014年起，马西坦和利奥西加的患病率增加可能反映了PH治疗的变化。尽管PH是一种罕见的疾病，患有PH的女性应该避免怀孕，特别是如果他们使用电子逆向拍卖，我们确定了暴露于ERA的怀孕。需要进行多数据库研究来评估这些药物对未出生婴儿的风险。
