Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Centre for Clinical Epidemiology, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
J Am Geriatr Soc. 2021 Apr;69(4):1012-1018. doi: 10.1111/jgs.16992. Epub 2021 Jan 11.
Direct oral anticoagulants (DOAC) are hydrophilic drugs with plasma levels inversely proportional to lean body mass. Sarcopenic patients with low muscle mass may be at risk for supra-therapeutic DOAC levels and bleeding complications. We therefore sought to examine the influence of lean body mass on DOAC levels in older adults with atrial fibrillation (AF).
A prospective cohort study was conducted with patients 65 years of age or more receiving rivaroxaban or apixaban for AF. Appendicular lean mass (ALM) was measured using a bioimpedance device and a dual X-ray absorptiometry scanner. DOAC levels were measured using a standardized anti-Xa assay 4 hours after (peak) and 1 hour before (trough) ingestion.
The cohort consisted of 62 patients (47% female, 77.0 ± 6.1 years). The prescribed DOACs were apixaban 2.5 mg (21%), apixaban 5 mg (53%), and rivaroxaban 20 mg (26%). Overall, 16% had supra-therapeutic DOAC levels at trough and 25% at peak. In the multivariable logistic regression model, lower ALM was independently associated with supra-therapeutic DOAC levels at trough (odds ratio per ↓ 1-kg 1.23, 95% confidence interval 1.02 to 1.49) and peak (odds ratio per ↓ 1-kg 1.18, 95% confidence interval 1.02 to 1.37). Addition of ALM to a model consisting of age, total body weight, and renal function resulted in improved discrimination for supra-therapeutic DOAC levels.
Our proof-of-concept study has identified an association between ALM and DOAC levels in older adults with AF. Further research is needed to determine the impact of ALM on bleeding complications and the potential role of ALM-guided dosing for sarcopenic patients.
直接口服抗凝剂（DOAC）是亲水性药物，其血浆水平与去脂体重成反比。肌肉量低的肌少症患者可能存在 DOAC 水平超治疗范围和出血并发症的风险。因此，我们研究了去脂体重对老年房颤（AF）患者 DOAC 水平的影响。
这是一项前瞻性队列研究，纳入了接受利伐沙班或阿哌沙班治疗 AF 的 65 岁及以上患者。使用生物阻抗设备和双能 X 线吸收仪测量四肢瘦体重（ALM）。在服药后 4 小时（峰值）和 1 小时前（谷值）使用标准化抗-Xa 测定法测量 DOAC 水平。
该队列包括 62 名患者（47%为女性，77.0±6.1 岁）。处方 DOAC 为阿哌沙班 2.5mg（21%）、阿哌沙班 5mg（53%）和利伐沙班 20mg（26%）。总体而言，16%的患者在谷值时 DOAC 水平超治疗范围，25%的患者在峰值时 DOAC 水平超治疗范围。多变量逻辑回归模型表明，ALM 较低与谷值时 DOAC 水平超治疗范围独立相关（每↓1kg 的比值比为 1.23，95%置信区间为 1.02 至 1.49）和峰值时 DOAC 水平超治疗范围独立相关（每↓1kg 的比值比为 1.18，95%置信区间为 1.02 至 1.37）。将 ALM 添加到由年龄、总体体重和肾功能组成的模型中，提高了对超治疗 DOAC 水平的区分能力。
我们的概念验证研究确定了老年 AF 患者 ALM 与 DOAC 水平之间存在关联。需要进一步研究以确定 ALM 对出血并发症的影响以及 ALM 指导剂量在肌少症患者中的潜在作用。
