Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (X.Y., J.W.I., C.G.N., N.D.S., P.A.N.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN.
Division of Health Care Policy and Research, Department of Health Sciences Research (X.Y., J.W.I., N.D.S.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN.
Circ Cardiovasc Qual Outcomes. 2020 Oct;13(10):e006515. doi: 10.1161/CIRCOUTCOMES.120.006515. Epub 2020 Oct 5.
Patients with atrial fibrillation and severely decreased kidney function were excluded from the pivotal non-vitamin K antagonist oral anticoagulants (NOAC) trials, thereby raising questions about comparative safety and effectiveness in patients with reduced kidney function. The study aimed to compare oral anticoagulants across the range of kidney function in patients with atrial fibrillation.
Using a US administrative claims database with linked laboratory data, 34 569 new users of oral anticoagulants with atrial fibrillation and estimated glomerular filtration rate ≥15 mL/(min·1.73 m) were identified between October 1, 2010 to November 29, 2017. The proportion of patients using NOACs declined with decreasing kidney function-73.5%, 69.6%, 65.4%, 59.5%, and 45.0% of the patients were prescribed a NOAC in estimated glomerular filtration rate ≥90, 60 to 90, 45 to 60, 30 to 45, 15 to 30 mL/min per 1.73 m groups, respectively. Stabilized inverse probability of treatment weighting was used to balance 4 treatment groups (apixaban, dabigatran, rivaroxaban, and warfarin) on 66 baseline characteristics. In comparison to warfarin, apixaban was associated with a lower risk of stroke (hazard ratio [HR], 0.57 [0.43-0.75]; <0.001), major bleeding (HR, 0.51 [0.44-0.61]; <0.001), and mortality (HR, 0.68 [0.56-0.83]; <0.001); dabigatran was associated with a similar risk of stroke but a lower risk of major bleeding (HR, 0.57 [0.43-0.75]; <0.001) and mortality (HR, 0.68 [0.48-0.98]; =0.04); rivaroxaban was associated with a lower risk of stroke (HR, 0.69 [0.51-0.94]; =0.02), major bleeding (HR, 0.84 [0.72-0.99]; =0.04), and mortality (HR, 0.73 [0.58-0.91]; =0.006). There was no significant interaction between treatment and estimated glomerular filtration rate categories for any outcome. When comparing one NOAC to another NOAC, there was no significant difference in mortality, but some differences existed for stroke or major bleeding. No relationship between treatments and falsification end points was found, suggesting no evidence for substantial residual confounding.
Relative to warfarin, NOACs are used less frequently as kidney function declines. However, NOACs appears to have similar or better comparative effectiveness and safety across the range of kidney function.
在关键性的非维生素 K 拮抗剂口服抗凝剂（NOAC）试验中排除了伴严重肾功能下降的心房颤动患者，这引发了关于肾功能下降患者中比较安全性和有效性的问题。本研究旨在比较不同范围的肾功能下心房颤动患者的口服抗凝剂。
使用具有相关实验室数据的美国行政索赔数据库，于 2010 年 10 月 1 日至 2017 年 11 月 29 日期间，确定了 34569 例新开始使用心房颤动且估算肾小球滤过率（eGFR）≥15mL/（min·1.73m）的口服抗凝剂患者。随着肾功能下降，使用 NOAC 的患者比例降低——eGFR≥90、60-90、45-60、30-45 和 15-30mL/min per 1.73m 组的患者中，分别有 73.5%、69.6%、65.4%、59.5%和 45.0%的患者处方了 NOAC。采用稳定逆概率处理加权法，在 66 项基线特征上平衡 4 个治疗组（阿哌沙班、达比加群、利伐沙班和华法林）。与华法林相比，阿哌沙班降低了卒中风险（危险比[HR]，0.57[0.43-0.75]；<0.001）、大出血风险（HR，0.51[0.44-0.61]；<0.001）和死亡率（HR，0.68[0.56-0.83]；<0.001）；达比加群与卒中风险相似，但降低了大出血风险（HR，0.57[0.43-0.75]；<0.001）和死亡率（HR，0.68[0.48-0.98]；=0.04）；利伐沙班降低了卒中风险（HR，0.69[0.51-0.94]；=0.02）、大出血风险（HR，0.84[0.72-0.99]；=0.04）和死亡率（HR，0.73[0.58-0.91]；=0.006）。任何结局的治疗和估计肾小球滤过率分类之间均无显著的交互作用。当比较一种 NOAC 与另一种 NOAC 时，死亡率没有显著差异，但卒中或大出血存在一些差异。未发现治疗方法与伪造终点之间存在关系，这表明没有实质性残余混杂的证据。
与华法林相比，随着肾功能下降，NOAC 的应用频率降低。然而，NOAC 在整个肾功能范围内似乎具有相似或更好的比较有效性和安全性。
