Haemostasis and Thrombosis Center, Ospedale di Cremona, Cremona, Italy.
Arianna Anticoagulazione Foundation, Bologna, Italy.
J Thromb Haemost. 2019 Jul;17(7):1064-1072. doi: 10.1111/jth.14457. Epub 2019 May 26.
Essentials Currently, DOACs are given at fixed doses and do not require laboratory monitoring. Direct oral anticoagulant-specific measurements were performed at trough and peak. Patients who developed bleeding events showed higher DOAC plasma levels at peak. This study suggests the need of a more accurate DOAC dose assessment.
Direct oral anticoagulants (DOACs) are administered at fixed dose. The aim of the study was to evaluate the relationship between DOAC C-trough or C-peak plasma levels and bleeding complications in patients with non-valvular atrial fibrillation (NVAF).
Five hundred sixty five consecutive naive NVAF patients were enrolled. The DOAC measurements at C-trough and at C-peak (available in 411 patients) were performed at steady state, within the first month of treatment. Major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and minor bleeding (MinB), occurring during 1 year of follow-up after blood sampling, were recorded. For each DOAC, interval of C-trough and C-peak levels was subdivided into four equal classes and results were attributed to these classes; the median values of results were also calculated.
Two hundred eight patients were on apixaban, 185 on dabigatran, and 172 on rivaroxaban. For 1-[qqqdeletezzz] year follow up for all patients, we observed: 19 MB (3.36%), 6 CRNMB (1.06%), and 47 MinB (8.31%). The prevalence of bleeding patients with anticoagulant levels in the upper classes of C-peak activity (II + III + IV) was higher than that in the lowest class. Normalized results of C-peak levels were higher in patients with bleeding than in those without bleeding.
Bleeding complications during DOAC treatment were more frequent among atrial fibrillation (AF) patients with higher C-peak anticoagulant levels. In addition to a previous study that showed an increased risk of thrombotic complications in the patients with low C-trough levels, this study seems to indicate that patients with NVAF on DOACs would need a more accurate definition of their optimal therapeutic window.
要点 当前，直接口服抗凝剂（DOAC）以固定剂量给药，且无需实验室监测。直接口服抗凝剂的特异性检测在谷值和峰值时进行。发生出血事件的患者在峰值时显示出更高的 DOAC 血浆水平。这项研究表明需要更准确地评估 DOAC 剂量。
直接口服抗凝剂（DOAC）以固定剂量给药。本研究旨在评估非瓣膜性心房颤动（NVAF）患者 DOAC 的 C 谷值或 C 峰值血浆水平与出血并发症之间的关系。
纳入了 565 例连续的 NVAF 初治患者。在治疗的第一个月内，在稳定状态下进行了 DOAC 的 C 谷值和 C 峰值（411 例患者可进行）检测。记录了在采血后 1 年随访期间发生的主要出血（MB）、临床相关非主要出血（CRNMB）和轻微出血（MinB）。对于每种 DOAC，将 C 谷值和 C 峰值水平的间隔分为四个相等的类别，并将结果归因于这些类别；还计算了结果的中位数。
208 例患者服用阿哌沙班，185 例患者服用达比加群，172 例患者服用利伐沙班。对于所有患者的 1 年随访，我们观察到：19 例 MB（3.36%）、6 例 CRNMB（1.06%）和 47 例 MinB（8.31%）。C 峰值活性（II+III+IV）较高的患者中，出血患者的比例高于最低类别的患者。与无出血的患者相比，出血患者的 C 峰值水平的归一化结果更高。
在 DOAC 治疗期间，AF 患者的 C 峰值抗凝剂水平较高时，出血并发症更常见。除了之前的一项研究表明低 C 谷值水平的患者发生血栓并发症的风险增加外，这项研究似乎表明，接受 DOAC 治疗的 NVAF 患者需要更准确地定义其最佳治疗窗口。
