Chan Yi-Hsin, Chao Tze-Fan, Lee Hsin-Fu, Yeh Yung-Hsin, Chang Shang-Hung, Kuo Chi-Tai, Lip Gregory Y H, Chen Shih-Ann
Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
JACC Asia. 2022 Feb 1;2(1):46-58. doi: 10.1016/j.jacasi.2021.11.006. eCollection 2022 Feb.
Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs.
The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes.
Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively.
At the cutoff values of eGFR of <15, 15-50, and >50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin.
The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages.
直接口服抗凝剂（DOACs）的随机试验采用Cockcroft-Gault（CG）公式来计算估计肾小球滤过率（eGFR），以确定DOACs的剂量。
作者旨在研究使用不同方程（CG、肾脏病饮食改良[MDRD]和慢性肾脏病流行病学协作组[CKD-EPI]公式）计算的eGFR之间的一致性/不一致性，以及它们对DOACs剂量和临床结局的影响。
使用来自台湾一家多中心医疗保健机构的医疗数据，其中包括39239例房颤患者。在这些患者中，分别有11185例和2323例接受了DOACs和华法林治疗。
在eGFR截止值<15、15 - 50和>50 mL/min时，MDRD与CG之间的一致性为78%，CKD-EPI与CG之间的一致性为81%。不同方程之间的不一致主要是由于高估，尤其是年龄>75岁且体重<50 kg的患者（MDRD为58.8%，CKD-EPI为50.9%）。在接受DOACs治疗且根据MDRD或CKD-EPI将剂量定义为“符合标签规定”的患者中，只有那些根据CG剂量“真正符合标签规定”的患者与华法林相比，大出血风险较低（调整后HR：0.34；95%CI：0.26 - 0.45）。
采用MDRD或CKD-EPI而非CG会导致DOACs剂量不当（主要是过量给药），这会削弱DOACs相对于华法林的优势。CG方程应作为计算eGFR和指导DOACs剂量的金标准。
