Khan Nazleen F, Kim Seoyoung C, Lee Su Been, Bykov Katsiaryna, Paik Julie M
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Harvard Medical School, Boston, MA.
Clin J Am Soc Nephrol. 2025 Jan 1;20(1):31-38. doi: 10.2215/CJN.0000000578. Epub 2024 Nov 19.
In patients with CKD and atrial fibrillation, we observed no difference in the rates of fracture between initiators of direct oral anticoagulant and warfarin. However, direct oral anticoagulant use relative to warfarin was associated with a lower risk of all-cause mortality.
Direct oral anticoagulant (DOAC) use has been associated with a lower risk of adverse events relative to warfarin in patients with atrial fibrillation. Little is known about the risk of fracture in association with anticoagulant therapy in patients with CKD.
We conducted a new user, active comparator cohort study in a United States-based commercial claims database spanning 2013 through 2020 to quantify the comparative risk of fracture associated with select DOACs (apixaban or rivaroxaban) versus warfarin. Individuals were required to have International Classification of Diseases diagnosis codes for CKD (stages 3–5) and atrial fibrillation during the 365-day baseline period before anticoagulant initiation. Primary analyses quantified nonvertebral fracture risk between patients initiating DOACs and warfarin using a 1:1 propensity score-matched design. Cox proportional hazards regression was used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) of nonvertebral fracture. Secondary analyses evaluated risks of hip fracture and all-cause mortality.
The 1:1 propensity score-matched population included 14,370 DOAC initiators and 14,370 warfarin initiators. The mean age at anticoagulant initiation was 77 years, and 45% were female. The HR for nonvertebral fracture comparing DOACs with warfarin was 1.12 (95% CI, 0.95 to 1.32), and the corresponding incidence rate difference per 1000 person-years was 3.55 (95% CI, −1.67 to 8.76). The HR and incidence rate difference comparing DOACs with warfarin were 0.98 (95% CI, 0.68 to 1.41) and −0.13 (95% CI, −2.52 to 2.25), respectively, for hip fracture and 0.91 (95% CI, 0.85 to 0.98) and −17.23 (95% CI, −29.49 to −4.96), respectively, for all-cause mortality.
In patients with CKD and atrial fibrillation, we did not observe a difference in the rates of fracture between DOAC and warfarin initiators. DOAC use relative to warfarin was associated with a lower risk of all-cause mortality.
在患有慢性肾脏病（CKD）和心房颤动的患者中，我们观察到直接口服抗凝剂起始使用者与华法林使用者之间的骨折发生率没有差异。然而，相对于华法林，使用直接口服抗凝剂与全因死亡率风险较低相关。
在心房颤动患者中，相对于华法林，使用直接口服抗凝剂（DOAC）与不良事件风险较低相关。对于CKD患者抗凝治疗相关的骨折风险知之甚少。
我们在美国一个涵盖2013年至2020年的商业索赔数据库中进行了一项新用户、活性对照队列研究，以量化与选定的DOAC（阿哌沙班或利伐沙班）相比华法林相关的骨折比较风险。在开始抗凝治疗前的365天基线期内，个体需要有CKD（3 - 5期）和心房颤动的国际疾病分类诊断代码。主要分析使用1:1倾向评分匹配设计量化开始使用DOAC和华法林的患者之间的非椎体骨折风险。使用Cox比例风险回归获得非椎体骨折的风险比（HRs）和95%置信区间（CIs）。次要分析评估髋部骨折风险和全因死亡率。
1:1倾向评分匹配人群包括14370名开始使用DOAC的患者和14370名开始使用华法林的患者。抗凝治疗开始时的平均年龄为77岁，45%为女性。比较DOAC与华法林的非椎体骨折HR为1.12（95%CI，0.95至1.32），每1000人年相应的发病率差异为3.55（95%CI，-1.67至8.76）。比较DOAC与华法林的髋部骨折HR和发病率差异分别为0.98（95%CI，0.68至1.41）和-0.13（95%CI，-2.52至2.25），全因死亡率的HR和发病率差异分别为0.91（95%CI，0.85至0.98）和-17.23（95%CI，-29.49至-4.96）。
在患有CKD和心房颤动的患者中，我们没有观察到开始使用DOAC和华法林的患者之间骨折发生率的差异。相对于华法林，使用DOAC与全因死亡率风险较低相关。
