Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
Division of Clinical Chemistry, National Cerebral and Cardiovascular Center, Osaka, Japan.
PLoS One. 2019 Mar 21;14(3):e0214132. doi: 10.1371/journal.pone.0214132. eCollection 2019.
The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form.
Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)].
The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.
已报道压碎片剂的利伐沙班浓度低于非压碎片剂的浓度。然而，尚未研究利伐沙班细颗粒的浓度。本研究比较了急性脑卒中患者中利伐沙班细颗粒、片剂和压碎片剂的抗凝强度，以评估每种形式的疗效。
纳入 2012 年 4 月至 2017 年 9 月期间开始服用利伐沙班的年龄均超过 75 岁的住院急性脑卒中患者。根据抗因子 Xa 显色测定法，在治疗开始后 5 天中位数抽取服药前（C0h）和服药后 4 小时（C4h）的血样，以测量浓度（C0h、C4h）。114 例患者（49 名女性，83±5 岁）中，97 例为缺血性脑卒中，9 例为短暂性脑缺血发作，8 例为脑出血。利伐沙班中位起始给药时间为发病后 7 天。其中，38 例患者给予 15mg 剂量，76 例患者给予 10mg 剂量。在 15mg 剂量组中，细颗粒组的 C0h 明显高于压碎片剂组，与片剂组无显著差异[C0h：27.6±6.8 比 4.0±4.1（P=0.01）比 33.3±25.2ng/ml，（P=0.51）]，C4h 也如此[223.0±66.6 比 103.0±79.5（P=0.02）比 229.5±121.6ng/ml（P=0.88）]。在 10mg 剂量组中，细颗粒组的 C0h 明显高于压碎片剂组，与片剂组相当[C0h：23.2±7.9 比 7.5±6.2（P<0.01）比 19.0±15.8ng/ml，（P=0.35）]，C4h 也如此[C4h：150.7±85.4 比 85.1±46.8（P<0.01）比 189.8±92.7ng/ml（P=0.18）]。
细颗粒的利伐沙班浓度与片剂组一致，且高于压碎片剂组。
