Faculdade de Medicina, Universidade de Lisboa, Portugal.
Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Portugal; Serviço de Cardiologia, Hospital Universitário de Santa Maria (CHLN), CAML, Lisboa, Portugal; Cardiovascular da Universidade de Lisboa - CCUL (CCUL@RISE), Faculdade de Medicina, Universidade de Lisboa, Portugal.
Int J Cardiol. 2022 Sep 1;362:76-82. doi: 10.1016/j.ijcard.2022.04.062. Epub 2022 May 2.
Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia among older patients, associated with thromboembolic events. Direct Oral Anticoagulants (DOAC) are the treatment of choice for most patients, but its use may have risks on standard dose. However, it is still unclear the effects related with the use of a lower dose off labelled DOAC.
We conducted a systematic review and meta-analysis to assess the effects of off-label underdose use of DOAC in patients with AF.
MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO databases and EMBASE were searched for observational longitudinal studies evaluating the outcomes on off label underdosed patients compared with standard dosed patients with AF. We performed a random-effects meta-analysis to estimate the pooled Hazard Ratios (HR) with 95%Cis.
Eighteen cohort studies evaluating 237,533 patients with AF were included. Off-label underdose DOAC use is associated with higher risk of all-cause mortality [HR = 1.27 (95%CI 1.09-1.48)] and cardiovascular composite outcomes [HR = 1.32 (95%CI 1.08-1.62)], when compared with standard dose DOAC use. The effects in thromboembolic events [HR = 1.14 (95%CI 1.00-1.31)], major bleeding [HR = 1.02 (95%CI 0.91-1.15)], and composite of ischemic and bleeding events [HR = 1.22 (95%CI 0.79-1.88)] were not statistically significant. The certainty in the evidence was low or very low.
Off label underdose DOAC use is associated with higher risk of all-cause mortality and cardiovascular composite outcomes, compared with standard dose.
心房颤动（AF）是老年患者中最常见的心律失常，与血栓栓塞事件有关。直接口服抗凝剂（DOAC）是大多数患者的首选治疗方法，但标准剂量的使用可能存在风险。然而，关于使用较低剂量的非标签 DOAC 的相关效果仍不清楚。
我们进行了系统评价和荟萃分析，以评估 AF 患者使用非标签低剂量 DOAC 的效果。
我们检索了 MEDLINE、Cochrane 对照试验中心注册库、PsycINFO 数据库和 EMBASE，以评估评估非标签低剂量患者与 AF 标准剂量患者相比的结局的观察性纵向研究。我们进行了随机效应荟萃分析，以估计合并危险比（HR）及其 95%置信区间（CI）。
纳入了 18 项评估 237533 例 AF 患者的队列研究。与标准剂量 DOAC 相比，非标签低剂量 DOAC 的使用与全因死亡率[HR=1.27（95%CI 1.09-1.48）]和心血管复合结局[HR=1.32（95%CI 1.08-1.62）]的风险增加相关。与标准剂量 DOAC 相比，非标签低剂量 DOAC 的使用在血栓栓塞事件[HR=1.14（95%CI 1.00-1.31）]、大出血[HR=1.02（95%CI 0.91-1.15）]和缺血和出血复合事件[HR=1.22（95%CI 0.79-1.88）]方面的效果没有统计学意义。证据的确定性为低或极低。
与标准剂量相比，非标签低剂量 DOAC 的使用与全因死亡率和心血管复合结局的风险增加相关。
