Pisa Federica, Reinold Jonas, Lavikainen Piia, Koponen Marjaana, Taipale Heidi, Tanskanen Antti, Tiihonen Jari, Hartikainen Sirpa, Tolppanen Anna-Maija
School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.
Clin Epidemiol. 2021 Apr 22;13:295-307. doi: 10.2147/CLEP.S278306. eCollection 2021.
To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).
In the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005-2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression.
Altogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6-1.9) in non-users and 2.0 (95% CI 1.8-2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05-1.30) compared with non-users. The risk was higher for short duration of use (<14 weeks, HR 3.64, 95% CI 2.90-4.58) than for medium duration (14 to <64 weeks, HR 1.74, 95% CI 1.48-2.05) or ≥64 weeks' use (HR 1.23, 95% CI 1.08-1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03-2.08) compared with newer AEDs.
Our results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.
确定开始使用抗癫痫药物（AEDs）的阿尔茨海默病（AD）患者发生髋部骨折的风险。
在2005 - 2011年有临床确诊新发AD诊断的70719名芬兰社区居民的药物使用与AD（MEDALZ）队列中，我们使用国家处方登记册识别所有AEDs的新发使用者。AEDs分为 older（丙戊酸盐、卡马西平、氯硝西泮、苯妥英、左乙拉西坦、扑米酮）或 newer（普瑞巴林、加巴喷丁、奥卡西平、拉莫三嗪、托吡酯）。我们将每位使用者与2名非使用者进行匹配。从医疗保健护理登记册中识别出截至2015年的新发髋部骨折病例。我们使用Cox回归计算治疗加权风险比（HR）的逆概率及其95%置信区间。
共识别出5522名新发使用者，并与11044名非使用者进行匹配（两组中女性均占65%；中位年龄：81岁）。总共53.3%的使用者开始使用 newer AEDs（普瑞巴林79.8%，加巴喷丁10.2%），而46.7%的使用者开始使用 older AEDs（丙戊酸盐67.6%，卡马西平13.0%）。每100人年非使用者的年龄和性别调整后的髋部骨折发病率为1.8（95%CI 1.6 - 1.9），使用者为2.0（95%CI 1.8 - 2.2）。与非使用者相比，使用者发生髋部骨折的风险增加（HR 1.17，95%CI 1.05 - 1.30）。与相同随访时间的非使用者相比，使用时间短（<14周，HR 3.64，95%CI 2.90 - 4.58）的风险高于使用时间中等（14至<64周，HR 1.74，95%CI 1.48 - 2.05）或≥64周（HR 1.23，95%CI 1.08 - 1.40）。与 newer AEDs相比，older AEDs的HR为1.46（1.03 - 2.08）。
我们的结果表明，使用AEDs与AD患者髋部骨折风险增加相关。这些发现提示在为AD患者开AEDs之前应仔细考虑。由于癫痫患者跌倒和骨折风险增加，因此应仔细监测接受抗癫痫药物治疗的AD患者。
