Department of Geriatric Medicine, Northwest Clinics, Wilhelminalaan 12, 1815 JD, Alkmaar, The Netherlands.
Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands.
Drugs Aging. 2024 Sep;41(9):725-740. doi: 10.1007/s40266-024-01138-5. Epub 2024 Aug 14.
Both the prevalence of atrial fibrillation (AF) and its subsequent use of direct oral anticoagulants (DOACs) are rapidly increasing in patients of older age. In the absence of contra-indications, guidelines advocate anticoagulation based on the CHA2DS2-VASc score for all AF patients aged 75 and above. However, some practitioners are hesitant to prescribe anticoagulants to older and frail patients due to perceived elevated bleeding risks. This review delves into the comparative treatment outcomes of DOACs versus vitamin K antagonists (VKAs) in older patients with AF, particularly focusing on those of advanced age, frailty, increased risk of falling, chronic kidney disease (CKD), or with a history of major bleeding. Additionally, considerations on the use of off-label DOAC doses, the role of left atrial appendage (LAA) closure and future developments in factor XIa-inhibitors will be discussed.
While strong evidence supports the use of DOACs in the vital older patients with nonvalvular AF, it remains scant in frail patient groups. There is some evidence from non-randomized studies suggesting that the effect of DOACs compared with VKAs is consistent between frail and nonfrail patients. However, recent findings from a single randomized trial showed increased bleeding risks but comparable thromboembolic outcomes in frail individuals switching from VKAs to DOACs. In patients with an increased risk of falling, data suggest no relevant interaction of increased risk of falling on the effectiveness and safety of DOACs compared with warfarin. Resuming oral anticoagulants in patients with Af after major bleeding seems to be beneficial. Off-label low-dose DOAC is often prescribed to patients who were underrepresented in larger randomized trails because of an elevated risk of bleeding or overexposure to DOACs, but its effect on clinical outcomes remains uncertain.
DOACs are the recommended oral anticoagulant for vital older patients with AF. The scarcity of data backing DOAC use in frail individuals, those with renal impairments, or significant bleeding history underscores the necessity for further investigation. However, existing evidence suggests at least similar effectiveness and safety and potential benefits for DOACs in these patient subsets. Therefore, there is no reason to suggest these patients should be treated differently than the established guidelines regarding anticoagulation.
随着年龄的增长，房颤（AF）的患病率及其随后使用直接口服抗凝剂（DOACs）的情况迅速增加。在没有禁忌症的情况下，指南主张根据 CHA2DS2-VASc 评分对所有 75 岁及以上的 AF 患者进行抗凝治疗。然而，由于认为出血风险升高，一些医生不愿为老年和体弱患者开抗凝药。本综述深入探讨了 DOACs 与维生素 K 拮抗剂（VKAs）在老年 AF 患者中的治疗效果比较，特别是针对高龄、体弱、跌倒风险增加、慢性肾脏病（CKD）或有大出血史的患者。此外，还将讨论非标签 DOAC 剂量的使用、左心耳（LAA）封堵的作用以及因子 XIa 抑制剂的未来发展。
虽然有强有力的证据支持在有生命危险的非瓣膜性 AF 老年患者中使用 DOACs，但在体弱患者群体中证据仍然很少。一些非随机研究的证据表明，DOACs 与 VKAs 相比的效果在体弱和非体弱患者中是一致的。然而，最近一项单中心随机试验的结果显示，在从 VKAs 转换为 DOACs 的体弱患者中，出血风险增加，但血栓栓塞结局相似。在跌倒风险增加的患者中，数据表明与华法林相比，跌倒风险增加对 DOACs 的有效性和安全性没有相关影响。在大出血后重新开始口服抗凝剂治疗似乎对 AF 患者有益。对于因出血风险升高或 DOACs 暴露过度而在较大规模随机试验中代表性不足的患者，通常会开处方非标签低剂量 DOAC，但它对临床结局的影响仍不确定。
DOACs 是有生命危险的老年 AF 患者的推荐口服抗凝剂。在体弱患者、肾功能损害患者或有明显出血史的患者中使用 DOACs 的数据有限，这突显了进一步研究的必要性。然而，现有证据表明，DOACs 在这些患者亚组中至少具有相似的疗效和安全性以及潜在益处。因此，没有理由建议这些患者的抗凝治疗应与既定指南不同。
