Institute of Anaesthesiology, University and University Hospital Zurich, Zurich, Switzerland.
Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
Thromb Haemost. 2018 May;118(5):808-817. doi: 10.1055/s-0038-1639585. Epub 2018 Apr 3.
Rivaroxaban (RXA) is a direct oral factor Xa (Xa) antagonist with a short half-life and a fast onset and offset of effect. Before elective surgery, discontinuation is recommended with an interval of at least > 24 hours. In clinical practice, this is, however, not always sufficient to achieve a residual RXA plasma concentration deemed appropriate for surgery, defined as ≤ 50 mcg/L. Our study aimed at identifying factors associated with a higher-than-expected residual RXA plasma concentration in a large group of real-life patients.
This retrospective single-centre study included all patients taking RXA between 2012 and 2016 where RXA plasma concentration was determined by pharmacodynamic anti-Xa assay (518 measurements in 368 patients). Medical records were reviewed. Residual RXA plasma concentrations were then compared with expected values according to a pharmacokinetic model.
Residual RXA plasma concentration was significantly higher-than-expected in patients with atrial fibrillation, impaired kidney function (glomerular filtration rate [GFR] < 60 mL/min), CYP3A4-, CYP2J2- and PGP-inhibitory co-medication including amiodarone. Impaired kidney function (odds ratio [OR], 2.22, 95% confidence interval [CI], 1.30-3.78, = 0.003) and concomitant amiodarone intake (OR, 1.97, 95% CI, 1.04-3.72, = 0.036) were significantly associated with RXA plasma concentrations > 50 mcg/L at 24 to 48 hours after the last RXA intake.
In our group of real-life patients, impaired kidney function (GFR < 60 mL/min) and co-medication with amiodarone were independently associated with higher-than-expected residual RXA plasma concentrations. In these patients, standard intervals of RXA discontinuation may not always be sufficient before elective surgery and routine pre-operative determination of the residual RXA concentration could be advisable.
利伐沙班（RXA）是一种半衰期短、作用起效快、消除快的直接口服因子 Xa（Xa）拮抗剂。在择期手术前，建议停药间隔至少>24 小时。然而，在临床实践中，这并不总是足以达到认为适合手术的残留 RXA 血浆浓度，定义为≤50 mcg/L。我们的研究旨在确定在一大群真实患者中与高于预期的残留 RXA 血浆浓度相关的因素。
这是一项回顾性单中心研究，包括 2012 年至 2016 年间服用 RXA 的所有患者，其中 368 名患者的 518 次测量通过药效学抗-Xa 测定法确定 RXA 血浆浓度。审查了病历。然后根据药代动力学模型将残留的 RXA 血浆浓度与预期值进行比较。
患有心房颤动、肾功能受损（肾小球滤过率[GFR] <60 mL/min）、CYP3A4、CYP2J2 和 PGP 抑制性合并用药（包括胺碘酮）的患者，残留的 RXA 血浆浓度明显高于预期。肾功能受损（优势比[OR]，2.22，95%置信区间[CI]，1.30-3.78， = 0.003）和同时服用胺碘酮（OR，1.97，95% CI，1.04-3.72， = 0.036）与最后一次服用 RXA 后 24 至 48 小时残留的 RXA 血浆浓度>50 mcg/L 显著相关。
在我们的真实患者组中，肾功能受损（GFR <60 mL/min）和与胺碘酮联合用药与高于预期的残留 RXA 血浆浓度独立相关。在这些患者中，在择期手术前，标准的 RXA 停药间隔时间可能并不总是足够的，术前常规测定残留的 RXA 浓度可能是明智的。
