Zhang Qingxia, Ding Qian, Yan Suying, Yue Qun-Ying
Department of Pharmacy, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Disease, Beijing, China.
School of Pharmaceutical Science, Capital Medical University, Beijing, China.
Front Pharmacol. 2021 Dec 22;12:769251. doi: 10.3389/fphar.2021.769251. eCollection 2021.
The elderly are vulnerable to cardiovascular diseases and the incidence of atrial fibrillation (AF) and venous thromboembolism (VTE) increases significantly with age. Dabigatran is a commonly used new oral anticoagulant approved by the FDA for stroke prevention in patients with non-valvular AF and VTE treatment and prevention. Aspirin is commonly used as a preventive drug for cardiovascular diseases. AF and coronary heart disease share many risk factors, so these two diseases often coexist and thus dabigatran and aspirin are often combined in those people. The aim of this study was to analyze the clinical characteristics of fatal adverse events of dabigatran combined with aspirin in elderly patients, and to provide references for clinical rational use of drugs. Fatal adverse events related to the combined use of dabigatran and aspirin in elderly patients aged over 75 were extracted from the WHO global database of individual case safety reports (VigiBase). Well-documented reports, vigiGrade completeness score ≥0.80, or with an informative narrative, were analyzed with a focus on the clinical features of the cases. From 1968 up to January 19, 2020, there were 112 eligible reports in VigiBase from 13 countries, of which 33 were identified as well-documented. Of these 33, 19 were male (58%) and 14 were female (42%), the average age of the patients was 84 (75-95 years), with five cases of extreme weights (>100 kg in one case, <50 kg in four cases). There were 31 cases of death by internal bleeding (mainly 15 of gastrointestinal hemorrhage and 12 of intracranial hemorrhage) and two cases of the sudden death of unknown cause. Medication errors existed in 15 patients. The times to onset (TTO) was provided in 24 cases, ranging from 2 days to 4 years, and in 12 patients occurred within a month. Of the 31 patients with fatal bleeding events, 29 were associated with other factors that increase the risk of bleeding, such as diseases (hypertension, renal impairment, stroke, gastrointestinal related diseases, hypothyroidism, and cancer), drugs (antiplatelets, anticoagulants, thrombolytics, P glycoprotein substrates, non-steroidal anti-inflammatory drugs, hormones, selective serotonin reuptake inhibitors, and acetaminophen) and other factors (low body weights and alcohol consumption), and 21 of these contained two or more risk factors. The fatal adverse events associated with the combined use of dabigatran and aspirin in elderly patients were mainly serious bleeding events, which often occurred within 1 month. Most of these cases had medication errors and most of the patients had multiple diseases, medications, or other conditions at the same time that increase the risk of bleeding. It is suggested that prescription of dabigatran and aspirin in elderly patients should go along with alertness for medication errors, care for correct dose or control of other bleeding risk factors, and the combined medication time should be as short as possible to minimise serious adverse events.
老年人易患心血管疾病，心房颤动（AF）和静脉血栓栓塞（VTE）的发病率会随着年龄的增长而显著增加。达比加群是一种常用的新型口服抗凝剂，已获美国食品药品监督管理局（FDA）批准，用于非瓣膜性AF患者的卒中预防以及VTE的治疗和预防。阿司匹林通常用作心血管疾病的预防药物。AF和冠心病有许多共同的危险因素，因此这两种疾病常同时存在，故而达比加群和阿司匹林常在这些人群中联合使用。本研究的目的是分析达比加群联合阿司匹林在老年患者中致死性不良事件的临床特征，为临床合理用药提供参考。从世界卫生组织全球个体病例安全报告数据库（VigiBase）中提取75岁以上老年患者使用达比加群联合阿司匹林相关致死性不良事件。对记录完整的报告、vigiGrade完整性评分≥0.80或有详细叙述的报告进行分析，重点关注病例的临床特征。从1968年至2020年1月19日，VigiBase中有来自13个国家的112份合格报告，其中33份被确定为记录完整。在这33份报告中，男性19例（58%），女性14例（42%），患者平均年龄为84岁（75 - 95岁），有5例体重极端情况（1例体重>100 kg，4例体重<50 kg）。有31例死于内出血（主要是15例胃肠道出血和12例颅内出血），2例死因不明的猝死。15例患者存在用药错误。24例报告了发病时间（TTO），范围从2天到4年，12例在1个月内发病。在31例致命性出血事件患者中，29例与其他增加出血风险的因素相关，如疾病（高血压、肾功能损害、卒中、胃肠道相关疾病、甲状腺功能减退和癌症）、药物（抗血小板药、抗凝剂、溶栓剂、P糖蛋白底物、非甾体抗炎药、激素、选择性5-羟色胺再摄取抑制剂和对乙酰氨基酚）以及其他因素（低体重和饮酒），其中2个或更多风险因素的有21例。达比加群与阿司匹林联合使用在老年患者中相关致死性不良事件主要是严重出血事件，常发生在1个月内。这些病例大多存在用药错误，且大多数患者同时患有多种疾病、服用多种药物或存在其他增加出血风险的情况。建议老年患者使用达比加群和阿司匹林时应警惕用药错误，注意正确剂量或控制其他出血风险因素，联合用药时间应尽可能短，以尽量减少严重不良事件。
