Stalas Jennifer, Morris Robert, Bu Kun, von Bargen Kevin, Largmann Rebekah, Sanford Kathryn, Vandeventer Jacob, Han Weiru, Cheng Feng
Taneja College of Pharmacy, University of South Florida, 12901 Bruce B Downs Blvd Tampa, FL, 33612, USA.
Department of Biostatistics and Epidemiology, College of Public Health, University of South Florida, Tampa, FL, 33612, USA.
Heliyon. 2024 Feb 18;10(5):e26462. doi: 10.1016/j.heliyon.2024.e26462. eCollection 2024 Mar 15.
Deep vein thrombosis (DVT) has been reported as an adverse event for patients receiving combined oral contraceptives. Norethindrone/ethinyl estradiol (NET/EE) and drospirenone/ethinyl estradiol (DRSP/EE) are two commonly prescribed combined hormonal oral contraceptive agents used in the United States, differing in their progestin component.
The purpose of this study was to determine the association between the progestin component of a combined oral contraceptive and the risk of DVT in patients taking oral contraceptives for birth control using data derived from the FDA Adverse Event Reporting System (FAERS).
The risk of DVT was compared between patients that had taken NET/EE with those that had taken the DRSP/EE COC formulation for birth control. In addition, age was assessed as a possible confounder and the outcome severity for those diagnosed with DVT were compared between the two groups. Finally, association rule mining was utilized to identify possible drug-drug interactions that result in elevated DVT risk.
DVT was the fourth most commonly adverse event reported for patients taking DRSP/EE accounting for 8558 cases and the seventeenth most commonly reported adverse event for NET/EE accounting for 298 cases. Age was found to be a significant confounder for users of DRSP/EE with regards to DVT risk across all age groups assessed: 20<Age ≤ 30 (ROR = 1.33, 95% CI 1.23-1.45), 30<Age ≤ 40 (ROR = 2.16, 95% CI 1.98-2.35), and Age>40 (ROR = 3.69, 95% CI 3.37-4.04) However, there was only a statistically significant elevated risk in patients over 40 years of age taking NET/EE (ROR = 1.98, 95% CI 1.36-2.88). Patients that had taken DRSP/EE and the corticosteroid prednisone simultaneously had an approximately 3-fold increase in DVT risk (ROR = 2.77, 95% CI 2.43-3.15) relative to individuals that had only taken DRSP/EE.
Based on this analysis, there is a higher risk of developing DVT when taking DRSP/EE than when taking NET/EE as hormonal contraception. In addition, a possibly significant drug-drug interaction between different COC formulations and prednisone were identified. This interaction may result in elevated DVT risk due to a synergistic impairment of fibrinolysis and a decrease in plasmin production.
深静脉血栓形成（DVT）已被报道为接受复方口服避孕药患者的不良事件。炔诺酮/炔雌醇（NET/EE）和屈螺酮/炔雌醇（DRSP/EE）是美国常用的两种复方激素口服避孕药，它们的孕激素成分不同。
本研究的目的是利用美国食品药品监督管理局不良事件报告系统（FAERS）的数据，确定复方口服避孕药的孕激素成分与口服避孕药用于避孕的患者发生DVT风险之间的关联。
比较服用NET/EE和服用DRSP/EE复方口服避孕药用于避孕的患者发生DVT的风险。此外，将年龄作为可能的混杂因素进行评估，并比较两组中诊断为DVT患者的结局严重程度。最后，利用关联规则挖掘来识别可能导致DVT风险升高的药物相互作用。
DVT是服用DRSP/EE患者报告的第四大常见不良事件，共8558例；是服用NET/EE患者报告的第十七大常见不良事件，共298例。在所有评估的年龄组中，年龄被发现是服用DRSP/EE患者发生DVT风险的一个显著混杂因素：20＜年龄≤30岁（相对危险度[ROR]=1.33，95%置信区间[CI]1.23 - 1.45），30＜年龄≤40岁（ROR = 2.16，95% CI 1.98 - 2.35），年龄＞40岁（ROR = 3.69，95% CI 3.37 - 4.04）。然而，只有40岁以上服用NET/EE的患者存在统计学上显著升高的风险（ROR = 1.98，95% CI 1.36 - 2.88）。同时服用DRSP/EE和皮质类固醇泼尼松的患者发生DVT的风险相对于仅服用DRSP/EE的个体增加了约3倍（ROR = 2.77，95% CI 2.43 - 3.15）。
基于该分析，作为激素避孕措施，服用DRSP/EE时发生DVT的风险高于服用NET/EE时。此外，还识别出不同复方口服避孕药制剂与泼尼松之间可能存在显著的药物相互作用。这种相互作用可能由于纤维蛋白溶解的协同损害和纤溶酶产生的减少而导致DVT风险升高。
