Hasegawa Shiori, Matsui Toshinobu, Hane Yuuki, Abe Junko, Hatahira Haruna, Motooka Yumi, Sasaoka Sayaka, Fukuda Akiho, Naganuma Misa, Hirade Kouseki, Takahashi Yukiko, Kinosada Yasutomi, Nakamura Mitsuhiro
Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
Medical Database Co., Ltd., Shibuya-ku, Tokyo, Japan.
PLoS One. 2017 Jul 21;12(7):e0182045. doi: 10.1371/journal.pone.0182045. eCollection 2017.
Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3-71.4), 29.1 (23.5-35.9), 42.9 (32.3-57.0), 44.7 (32.7-61.1), and 38.6 (26.3-56.7), respectively. The medians (25%-75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3-314.0), 128.0 (27.0-279.0), 204.0 (44.0-660.0), 142.0 (41.3-344.0), and 16.5 (8.8-32.0) days, respectively. The 95% CIs of the WSP-β for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning.
雌激素 - 孕激素联合制剂（CEPs）与血栓栓塞（TE）副作用相关。本研究旨在使用日本药品不良反应报告（JADER）数据库评估TE的发生率。2004年4月至2014年11月期间JADER数据库中记录的不良事件从药品和医疗器械局（PMDA）网站（www.pmda.go.jp）获取。我们计算了疑似CEPs的报告比值比（RORs），分析了发病时间概况，并使用威布尔形状参数（WSP）评估了风险类型。此外，我们使用应用关联规则挖掘技术来发现未检测到的关系，如可能的风险因素。JADER数据库中包含的报告病例总数为338,224例。屈螺酮与炔雌醇（EE，Dro - EE）、炔诺酮与EE（Ne - EE）、左炔诺孕酮与EE（Lev - EE）、去氧孕烯与EE（Des - EE）以及炔诺孕酮与EE（Nor - EE）的RORs（95%置信区间，CI）分别为56.2（44.3 - 71.4）、29.1（23.5 - 35.9）、42.9（32.3 - 57.0）、44.7（32.7 - 61.1）和38.6（26.3 - 56.7）。Dro - EE、Ne - EE、Lev - EE、Des - EE和Nor - EE的发病时间中位数（25% - 75%）分别为150.0（75.3 - 314.0）、128.0（27.0 - 279.0）、204.0（44.0 - 660.0）、142.0（41.3 - 344.0）和16.5（8.8 - 32.0）天。Ne - EE、Lev - EE和Nor - EE的WSP - β的95% CI较低且不包括1。关联规则挖掘表明贫血患者在使用CEPs时发生TE的潜在风险。我们的结果表明，监测接受CEP治疗的患者是否发生TE很重要。建议仔细观察，尤其是对于使用Nor - EE的患者，这些信息可能有助于有效的治疗规划。
