Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
JAMA Netw Open. 2024 Mar 4;7(3):e243208. doi: 10.1001/jamanetworkopen.2024.3208.
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized.
To assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk.
DESIGN, SETTING, AND PARTICIPANTS: A population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration.
Concomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone.
The main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding.
There were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47).
This study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.
选择性 5-羟色胺再摄取抑制剂（SSRIs）是常用的抗抑郁药，与大出血的风险略有增加相关。然而，SSRIs 与口服抗凝剂（OACs）同时使用相关的出血风险尚未得到很好的描述。
评估与单独使用 OACs 相比，SSRIs 与 OACs 同时使用是否与大出血风险增加相关，描述这种风险随使用时间的变化情况，并确定改变这种风险的关键临床特征。
设计、地点和参与者：这是一项基于人群的嵌套病例对照研究，在 1998 年 1 月 2 日至 2021 年 3 月 29 日期间，对开始使用 OACs 的心房颤动患者进行。患者来自英国约 2000 家参与临床实践研究数据链接的普通诊所。通过风险集抽样，对于随访期间每例大出血病例，从病例和匹配的风险集中选择多达 30 个对照，这些对照按年龄、性别、队列进入日期和随访时间进行匹配。
SSRIs 与 OACs（直接 OACs 和维生素 K 拮抗剂[VKAs]）同时使用与单独使用 OACs 相比。
主要结局是出血住院或因出血导致的死亡的发生率比值比（IRR）。
共有 42190 例大出血（平均[标准差]年龄，74.2[9.3]岁；59.8%为男性）与 1156641 例对照（平均[标准差]年龄，74.2[9.3]岁；59.8%为男性）相匹配。与单独使用 OACs 相比，SSRIs 与 OACs 同时使用与大出血风险增加相关（IRR，1.33；95%CI，1.24-1.42）。风险在治疗的最初几个月达到峰值（使用的前 30 天：IRR，1.74；95%CI，1.37-2.22），并持续长达 6 个月。风险与年龄、性别、出血史、慢性肾脏病和 SSRIs 的效力无关。SSRIs 与直接 OACs 同时使用与直接 OACs 单独使用相比（IRR，1.25；95%CI，1.12-1.40），以及 SSRIs 与 VKAs 同时使用与 VKA 单独使用相比（IRR，1.36；95%CI，1.25-1.47）均存在相关性。
本研究表明，在心房颤动患者中，SSRIs 与 OACs 同时使用与单独使用 OACs 相比，大出血风险增加，需要密切监测和管理出血风险因素，尤其是在使用的最初几个月。
