Mosconi Maria Giulia, Maraziti Giorgio, Paciaroni Maurizio, Giustozzi Michela, Vedovati Maria Cristina, Bogliari Giulio, Urbini Chiara, Traballi Laura, Caso Valeria
Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy.
Emergency Department, Ospedale Città di Castello USL Umbria 1, Città di Castello (PG), Italy.
Eur Neurol. 2023;86(1):13-24. doi: 10.1159/000525407. Epub 2022 Sep 13.
The efficacy and safety profiles of nonrecommended direct oral anticoagulant (DOAC) doses in patients with nonvalvular atrial fibrillation (NVAF) are still undefined.
We searched for randomized controlled trials and observational studies that compared nonrecommended versus recommended doses of DOACs, published up to December 2021. Primary study outcomes were ischemic stroke/transient ischemic attack/systemic embolism (IS/TIA/SE) and major bleeding (MB). All-cause mortality was a secondary outcome. We determined pooled odds ratios (ORs) between groups of patients with a random-effect model. Twenty-three studies with 175,801 patients were included. Nonrecommended doses were associated with a higher risk of IS/TIA/SE and all-cause mortality, but not of MB as compared to recommended doses of DOACs (OR 1.25 [95% CI: 1.14-1.38], OR 1.69 [95% CI: 1.31-2.18] and OR 1.10 [95% CI: 0.93-1.31], respectively). The nonrecommended low dose was associated with an increased risk of IS/TIA/SE and all-cause death (OR 1.21 [95% CI: 1.05-1.39] and OR 1.66 [95% CI: 1.18-2.35], respectively) but not of MB (OR 1.01 [95% CI: 0.83-1.22] as compared to recommended doses. Subgroup analysis of nonrecommended low doses of DOACs showed a nonsignificant increase in IS/TIA/SE in Asians (OR 1.17 [95% CI: 0.89-1.54] vs. non-Asian (OR 1.21 [95% CI: 1.07-1.36]).
Compared with recommended doses, nonrecommended low doses of DOACs increase the risk of ischemic events without decreasing the risk of bleeding. For Asians, the efficacy of DOACs seemed preserved despite the nonrecommended low-dose prescription. Clinicians should carefully adhere to recommended DOAC prescription advice in managing NVAF patients.
非瓣膜性心房颤动（NVAF）患者中未推荐的直接口服抗凝剂（DOAC）剂量的疗效和安全性仍不明确。
我们检索了截至2021年12月发表的比较未推荐与推荐剂量DOAC的随机对照试验和观察性研究。主要研究结局为缺血性卒中/短暂性脑缺血发作/全身性栓塞（IS/TIA/SE）和大出血（MB）。全因死亡率为次要结局。我们采用随机效应模型确定患者组之间的合并比值比（OR）。纳入了23项研究，共175,801例患者。与推荐剂量的DOAC相比，未推荐剂量与IS/TIA/SE和全因死亡率风险较高相关，但与MB风险无关（OR分别为1.25 [95% CI：1.14 - 1.38]、OR 1.69 [95% CI：1.31 - 2.18]和OR 1.10 [95% CI：0.93 - 1.31]）。未推荐的低剂量与IS/TIA/SE和全因死亡风险增加相关（OR分别为1.21 [95% CI：1.05 - 1.39]和OR 1.66 [95% CI：1.18 - 2.35]），但与MB风险无关（与推荐剂量相比，OR为1.01 [95% CI：0.83 - 1.22]）。对未推荐的低剂量DOAC进行亚组分析显示，亚洲人IS/TIA/SE的增加无统计学意义（OR 1.17 [95% CI：0.89 - 1.54] 对比非亚洲人（OR 1.21 [95% CI：1.07 - 1.36]）。
与推荐剂量相比，未推荐的低剂量DOAC增加了缺血性事件的风险，而未降低出血风险。对于亚洲人，尽管使用了未推荐的低剂量处方，DOAC的疗效似乎仍得以保留。临床医生在管理NVAF患者时应严格遵循推荐的DOAC处方建议。
