Data Analysis of the Risks of Abnormal Female Reproductive System Haemorrhages Induced by Novel Oral An- ticoagulants Based on FAERS / 中国药房

ABSTRACT

OBJECTIVE：To eva luate the risk of abno rmal female reproductive system haemorrhage induced by novel oral anticoagulants （NOACs）. METHODS ：The abnormal female reproductive system haemorrhage reports induced by 4 kinds of NOACs as “dabigatran etexilate ”，“rivaroxaban”，“apixaban”and“edoxaban”were used as the first suspected dugs to collected from FDA adverse event reporting system （FAERS）database during Jan. 1st，2004-May 31st，2019. The report odd ratio （ROR） method was used to detect the signal of abnormal female reproductive system haemorrhage induced by NOACs. RESULTS ：A total of 2 658 adverse events related to abnormal female reproductive system haemorrhage were collected from FAERS database ， involving 330 reports of dabigatran etexilate ，2 049 reports of rivaroxaban ，267 reports of apixaban ，and 12 reports of edoxaban. The abnormal female reproductive system haemorrhage caused by dabigatran etexilate ，apixaban and edoxaban mainly occurred in patients aged 75 and older ，accounting for 37.27％，36.70％ and 58.33％ respectively；that of rivaroxaban mainly occurred in patients with 45-64 years old ，accounting for 33.04％. The incidence of severe adverse events （SAE）induced by dabigatran etexilate，rivaroxaban，apixaban and edoxaban were 96.36％，84.53％，47.19％ and 58.33％，respectively. All of patients in the included reports were mainly hospitalized and hospitalization stay wa s prolonged ，accounting for 64.78％，90.01％，86.51％ and 71.43％ ，respectively. A total of 12 suspected signals were detected，involving cervix uteri ，fallopian tube ，ovary，pelvis cavity，uterus，vagina，urinary tract ，etc. Among them ，there were 11 positive signals of rivaroxaban ，and the bleeding events were concentrated in vaginal hematoma [ROR ＝12.07， 药。95％CI（8.51，17.12）]，postmenopausal hemorrhage [ROR ＝ 9.89，95％CI（8.31，11.77）]，pelvic hematoma [ROR ＝7.68，95％CI（5.66，10.43）]. There were 4，4 and 2 suspicious signals for dabigatran etexilate ，apixaban and edoxaban. The main bleeding events of both apixaban [ ROR＝5.18，95％CI（1.81，5.85）] and edoxaban [ROR ＝48.19，95％CI（6.76，343.77）] were vaginal hematoma ；dabigatran etexilate-induced pelvic hematoma [ROR ＝ 12.56，95％CI（8.92，17.70）] had the strongest signal ，followed by urinary tract bleeding [ROR ＝5.41，95％CI（3.34，8.76）] and pelvic hemorrhage [ ROR＝2.53，95％CI（1.88，3.40）]. CONCLUSIONS ：Totally 4 kinds of NOACs can cause abnormal female reproductive system haemorrhage ，and the incidence of SAE is high ，of requiring hospitalization or prolonging hospitalization time. The risk of haemorrhage in rivaroxaban is the highest ，usually manifesting as vaginal hematoma ，postmenopausal hemorrhage and pelvic hematoma. Dabigatran etexilate mainly induce pelvic hematoma ，while apixaban and edoxaban are mainly cause vaginal hematoma.