Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Br J Clin Pharmacol. 2011 Nov;72(5):798-805. doi: 10.1111/j.1365-2125.2011.04004.x.
The aim of this study was to investigate the effects of co-medication with selective serotonin re-uptake inhibitors (SSRIs) on overanticoagulation during acenocoumarol maintenance treatment.
All subjects from The Rotterdam Study who received acenocoumarol maintenance treatment between April 1 1991 and September 9 2009 were followed for the event of an international normalized ratio (INR) ≥6, until death, end of treatment or end of the study period. With the Andersen-Gill extension of the Cox proportional hazards model, risks for repeated events of overanticoagulation in relation to concomitant SSRI use were calculated.
The risk for overanticoagulation during acenocoumarol maintenance treatment was increased in combination with fluvoxamine (HR 2.63, 95% CI 1.49, 4.66) and venlafaxine (HR 2.19, 95% CI 1.21, 3.99). There was no increase in risk for the other SSRIs, but numbers of exposed cases were low for all SSRIs except paroxetine.
Fluvoxamine and venlafaxine were associated with a more than double risk of INR values ≥6 in acenocoumarol treated subjects.
本研究旨在探讨选择性 5-羟色胺再摄取抑制剂（SSRIs）与华法林维持治疗中过度抗凝之间的联合用药效应。
所有 1991 年 4 月 1 日至 2009 年 9 月 9 日期间接受华法林维持治疗的鹿特丹研究受试者，在 INR（国际标准化比值）≥6 时进行随访，直至死亡、治疗结束或研究期末。采用 Andersen-Gill 扩展 Cox 比例风险模型，计算与同时使用 SSRIs 相关的重复过度抗凝事件的风险。
华法林维持治疗期间与氟伏沙明（HR 2.63，95%CI 1.49，4.66）和文拉法辛（HR 2.19，95%CI 1.21，3.99）联合使用时，过度抗凝的风险增加。其他 SSRIs 的风险没有增加，但除帕罗西汀外，所有 SSRIs 的暴露病例数都较低。
氟伏沙明和文拉法辛与 INR 值≥6 的华法林治疗受试者的风险增加超过两倍有关。
