Application of direct-acting oral anticoagulants in chronic kidney disease patients complicated with atrial fibrillation

doi:10.3877/cma.j.issn.2095-3216.2023.01.005

Abstract

Abstract:

Chronic kidney disease (CKD) is closely related to atrial fibrillation. The prevalence of atrial fibrillation in CKD patients is significantly higher than that in the general population, and the risk of cardio-cerebrovascular disease and all-cause death in these patients is also significantly higher. At present, studies have shown that anticoagulation therapy is beneficial for patients with atrial fibrillation complicated with mild to moderate renal dysfunction, while there is still controversy about whether anticoagulation therapy should be performed for patients with atrial fibrillation complicated with severe renal insufficiency or undergoing maintenance dialysis. This article reviewed the research progress in the characteristics, choice, dosage, efficacy and safety of direct-acting oral anticoagulants (DOACs), in order to provide a reference for the clinical work of using DOACs to treat CKD patients with atrial ibrillation.

Key words: Chronic kidney disease, Atrial fibrillation, Direct-acting oral anticoagulation, Anticoagulation therapy

Xiaojing Shi, Xiaole Su, Lihua Wang. Application of direct-acting oral anticoagulants in chronic kidney disease patients complicated with atrial fibrillation[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2023, 12(01): 26-31.

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References 46

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特征参数	达比加群酯	利伐沙班	阿哌沙班	依杜沙班	贝曲沙班
作用靶点	凝血酶/Ⅱ因子	Ⅹa因子	Ⅹa因子	Ⅹa因子	Ⅹa因子
生物利用度	6.5%	66%(不与食物同服)，80%～100%(与食物同服)	60%	50%	34%
血药浓度达峰时间	2～3 h	2～4 h	3～4 h	1～2 h	3～4 h
半衰期	12～17 h	5～9 h(年龄≥75岁，11～13 h)	10～14 h	10～14 h	19～27 h
血浆蛋白结合率(%)	35	95	87	55	60
代谢途径	肝脏经酯酶水解为主，不依赖CYP3A4途径代谢	1/3以活性药物原型经肾脏清除，2/3经CYP3A4途径代谢	经CYP3A4途径代谢	极少部分(约4%)经CYP3A4代谢	不依赖于CYP3A4代谢，大部分药物原型通过胆汁排泄
肾清除率	80%	35%	27%	50%	11%
相互作用	P-gp抑制剂	CYP3A4和P-gp抑制剂	CYP3A4抑制剂	CYP3A4和P-gp抑制剂	仅强P-gp抑制剂
透析度	50%～60%	否	14%	否	未被研究
逆转剂	Idarucizumab	Andexanet alfa	Andexanet alfa	Andexanet alfa(尚未被批准)	Andexanet alfa(尚未被批准)

特征参数	达比加群酯	利伐沙班	阿哌沙班	依杜沙班	贝曲沙班
作用靶点	凝血酶/Ⅱ因子	Ⅹa因子	Ⅹa因子	Ⅹa因子	Ⅹa因子
生物利用度	6.5%	66%(不与食物同服)，80%～100%(与食物同服)	60%	50%	34%
血药浓度达峰时间	2～3 h	2～4 h	3～4 h	1～2 h	3～4 h
半衰期	12～17 h	5～9 h(年龄≥75岁，11～13 h)	10～14 h	10～14 h	19～27 h
血浆蛋白结合率(%)	35	95	87	55	60
代谢途径	肝脏经酯酶水解为主，不依赖CYP3A4途径代谢	1/3以活性药物原型经肾脏清除，2/3经CYP3A4途径代谢	经CYP3A4途径代谢	极少部分(约4%)经CYP3A4代谢	不依赖于CYP3A4代谢，大部分药物原型通过胆汁排泄
肾清除率	80%	35%	27%	50%	11%
相互作用	P-gp抑制剂	CYP3A4和P-gp抑制剂	CYP3A4抑制剂	CYP3A4和P-gp抑制剂	仅强P-gp抑制剂
透析度	50%～60%	否	14%	否	未被研究
逆转剂	Idarucizumab	Andexanet alfa	Andexanet alfa	Andexanet alfa(尚未被批准)	Andexanet alfa(尚未被批准)

药物(肾脏排泄)	肾小球滤过率[ml/(min·1.73 m²)]				透析人群
药物(肾脏排泄)	≥50	30～49	15～29	<15	透析人群
优选药物	DOAC	DOAC	VKA或DOAC	VKA(仅高危人群^a)	VKA(仅高危人群^a)
VKA	维持TTR^b>70%	维持TTR>70%	维持TTR>70%	维持TTR>70%	维持TTR>70%
达比加群(80%)	150 mg 2次/d或110 mg 2次/d(年龄≥80岁或口服维拉帕米或有出血的风险)	150 mg 2次/d或者110 mg 2次/d(年龄≥80岁或口服维拉帕米或有出血的风险)	AHA：75 mg 2次/d^c ESC^d：不使用	不使用	不使用
利伐沙班(35%)	20 mg 1次/d	15 mg 1次/d	15 mg 1次/d	不使用	不使用
阿哌沙班(27%)	5 mg 2次/d；满足以下两项以上减量为2.5 mg 2次/d：年龄≥80岁或体重≤60公斤或血肌酐≥1.5 mg/dl	5 mg 2次/d；满足以下两项以上减量为2.5 mg 2次/d：年龄≥80岁或体重≤60公斤或血肌酐≥1.5 mg/dl	2.5 mg 2次/d	AHA：2.5 mg 2次/d^c ESC：不使用^d	AHA：2.5 mg 2次/d^c ESC：不使用^d
依度沙班(50%)	60 mg 1次/d；满足以下两项以上减量为30 mg 1次/d：体重≤60 kg或CrCl 30～50 ml/min或口服维拉帕米，决奈达隆或奎尼丁	30 mg 1次/d	30 mg 1次/d	不使用	不使用

药物(肾脏排泄)	肾小球滤过率[ml/(min·1.73 m²)]				透析人群
药物(肾脏排泄)	≥50	30～49	15～29	<15	透析人群
优选药物	DOAC	DOAC	VKA或DOAC	VKA(仅高危人群^a)	VKA(仅高危人群^a)
VKA	维持TTR^b>70%	维持TTR>70%	维持TTR>70%	维持TTR>70%	维持TTR>70%
达比加群(80%)	150 mg 2次/d或110 mg 2次/d(年龄≥80岁或口服维拉帕米或有出血的风险)	150 mg 2次/d或者110 mg 2次/d(年龄≥80岁或口服维拉帕米或有出血的风险)	AHA：75 mg 2次/d^c ESC^d：不使用	不使用	不使用
利伐沙班(35%)	20 mg 1次/d	15 mg 1次/d	15 mg 1次/d	不使用	不使用
阿哌沙班(27%)	5 mg 2次/d；满足以下两项以上减量为2.5 mg 2次/d：年龄≥80岁或体重≤60公斤或血肌酐≥1.5 mg/dl	5 mg 2次/d；满足以下两项以上减量为2.5 mg 2次/d：年龄≥80岁或体重≤60公斤或血肌酐≥1.5 mg/dl	2.5 mg 2次/d	AHA：2.5 mg 2次/d^c ESC：不使用^d	AHA：2.5 mg 2次/d^c ESC：不使用^d
依度沙班(50%)	60 mg 1次/d；满足以下两项以上减量为30 mg 1次/d：体重≤60 kg或CrCl 30～50 ml/min或口服维拉帕米，决奈达隆或奎尼丁	30 mg 1次/d	30 mg 1次/d	不使用	不使用

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