Abstract：
OBJECTIVE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls.
METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province.
RESULTS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group.
CONCLUSIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.
METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province.
RESULTS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group.
CONCLUSIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.
摘要：
目的：尽管癫痫患者使用抗癫痫药物（ASM）的直接口服抗凝剂（DOAC）的处方正在增加，国际指南提出了严格的限制,因为这可能导致药物相互作用.然而,目前关于其临床相关性的证据仍然很少。这次回顾，病例对照研究评估了现实世界中涉及DOAC-ASM联合治疗的缺血/出血性事件和癫痫发作的频率，与DOAC和ASM单一疗法相比，在年龄和性别匹配的对照中。
方法：从亚历山德里亚省（意大利）药学服务机构的数据库中提取了至少6个月同时使用DOAC和ASM治疗的患者的数据。排除后，病例组包括124例患者，44丙戊酸（VPA）和80左乙拉西坦（LEV）伴随DOAC，并与DOAC对照组和ASM对照组进行比较。临床和实验室数据是从同一省医院的电子档案中提取的。
结果：在病例组中观察到2例（1.6％）缺血性事件和2例（1.6％）大出血事件。DOAC对照组发生4例（3.2%）缺血事件，无出血事件。病例组（服用DOAC的合并LEV或VPA患者）和DOAC对照组之间的缺血和出血性事件无统计学差异，病例组与ASM对照组的癫痫发作复发率无差异。
结论：虽然本研究有一定的局限性，主要是小样本量，我们的研究结果表明,在现实环境中,LEV和VPA伴随治疗均不显著影响DOAC的效果.
方法：从亚历山德里亚省（意大利）药学服务机构的数据库中提取了至少6个月同时使用DOAC和ASM治疗的患者的数据。排除后，病例组包括124例患者，44丙戊酸（VPA）和80左乙拉西坦（LEV）伴随DOAC，并与DOAC对照组和ASM对照组进行比较。临床和实验室数据是从同一省医院的电子档案中提取的。
结果：在病例组中观察到2例（1.6％）缺血性事件和2例（1.6％）大出血事件。DOAC对照组发生4例（3.2%）缺血事件，无出血事件。病例组（服用DOAC的合并LEV或VPA患者）和DOAC对照组之间的缺血和出血性事件无统计学差异，病例组与ASM对照组的癫痫发作复发率无差异。
结论：虽然本研究有一定的局限性，主要是小样本量，我们的研究结果表明,在现实环境中,LEV和VPA伴随治疗均不显著影响DOAC的效果.
