Dabigatran Concentration: Variability and Potential Bleeding Prediction In "Real-Life" Patients With Atrial Fibrillationl
Dabigatran Concentration: Variability and Potential Bleeding Prediction In "Real-Life" Patients With Atrial Fibrillationl
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DOI：
10.1111/bcpt.12417
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发表时间：
2015-11-01
影响因子：
3.1
通讯作者：
Mavri, Alenka
中科院分区：
文献类型：
--
作者：
Sinigoj, Petra;Malmstrom, Rickard E.;Mavri, Alenka
目前不建议接受达比加群治疗的患者进行常规实验室监测，尽管其血浆浓度有相当大的变化。然而，在某些临床情况下，测量达比加群效应可能是可取的。我们的目的是评估达比加群谷和峰浓度的可变性，并探讨达比加群浓度与不良事件之间的潜在关系。我们纳入了44例房颤患者，他们开始使用达比加群150mg （D150）或110mg （D110）治疗，每日两次。他们在达比加群开始治疗后2-4周和6-8周采集了170份波谷和波峰血样。血浆达比加群浓度采用LC-MS/MS法测定，并通过选定的凝血试验间接测定。与D150患者相比，D110患者年龄较大（74 +/- 7岁对68 +/- 6岁），肌酐清除率较低（68 +/- 21岁对92 +/- 24 mL/min）， CHA(2)DS(2)- vasc评分较高（3.1 +/- 1.3对2.3 +/- 0.9）（均p < 0.05），但两者在波谷和波峰样品中的达比加群浓度相似。达比加群浓度波谷变化小于波峰变化（17.0 +/- 13.6% vs 26.6 +/- 19.2%, p = 0.02）。在12个月的随访中，D150组有4例，D110组有6例出现轻微出血。没有大出血或血栓栓塞事件。出血患者达比加群平均谷浓度显著高于无出血患者（93 +/- 36 vs 72 +/- 62 μ g/L, p = 0.02），而达比加群峰值值无预测价值。根据指南选择的达比加群剂量产生了适当的谷浓度和可接受的重复性。高谷浓度可能使患者易发生轻微出血的危险。
Routine laboratory monitoring is currently not recommended in patients receiving dabigatran despite its considerable variation in plasma concentration. However, in certain clinical situations, measurements of the dabigatran effect may be desirable. We aimed to assess the variability of dabigatran trough and peak concentration and explore the potential relationship between dabigatran concentration and adverse events. We included 44 patients with atrial fibrillation who started treatment with dabigatran 150 mg (D150) or 110 mg (D110) twice daily. They contributed 170 trough and peak blood samples that were collected 2-4 and 6-8 weeks after dabigatran initiation. Plasma dabigatran concentration was measured by LC-MS/MS and indirectly, by selected coagulation tests. D110 patients were older (74 +/- 7 versus 68 +/- 6 years), had lower creatinine clearance (68 +/- 21 versus 92 +/- 24 mL/min) and higher CHA(2)DS(2)-VASc score (3.1 +/- 1.3 versus 2.3 +/- 0.9) compared to D150 patients (all p < 0.05), but both had similar dabigatran concentrations in both trough and peak samples. Dabigatran concentrations varied less in trough than in peak samples (17.0 +/- 13.6 versus 26.6 +/- 19.2%, p = 0.02). During the 12-month follow-up, 4 patients on D150 and 6 on D110 suffered minor bleeding. There was no major bleeding or thromboembolic event. Patients with bleeding had significantly higher average trough dabigatran concentrations (93 +/- 36 versus 72 +/- 62 mu g/L, p = 0.02) than patients without bleeding, while peak dabigatran values had no predictive value. Dabigatran dose selection according to the guidelines resulted in appropriate trough concentrations with acceptable repeatability. High trough concentrations may predispose patients to the risk of minor bleeding.