服用达比加群酯的非瓣膜病心房颤动患者活化部分凝血活酶时间的调查

The level of activated partial thromboplastin time levels in nonvalvular atrial fibrillation patients treated with dabigatran

目的调查服用达比加群酯的非瓣膜病心房颤动(NVAF)患者达比加群酯谷浓度时活化部分凝血活酶时间(APTT)的分布范围及其相关影响因素,并对左心房血流不同状态下此APTT是否存在差异做初步探讨。方法本研究为横断面调查研究。连续入选2018年8月至2020年10月在南京医科大学第一附属医院心内科住院的服用达比加群酯的NVAF患者。入选患者在入院前均已规律服用达比加群酯至少3周。入院后在达比加群酯处于谷浓度时进行APTT检测。根据Cockcroft-Gault公式计算患者的肌酐清除率(CCR)。多重线性回归分析达比加群酯谷浓度时APTT的影响因素。单因素方差分析左心房血流不同状态下达比加群酯谷浓度时的APTT是否存在差异。结果共入选患者584例,年龄为(60.3±10.7)岁,其中男397例(68.0%,397/584)。所有患者CHA_(2)DS_(2)-VASc评分为(1.7±1.4)分,HAS-BLED评分为(1.2±0.9)分。581例患者服用达比加群酯110 mg,每日2次,另3例患者服用达比加群酯150 mg,每日2次。达比加群酯谷浓度时APTT在正常下限以下的患者1例;APTT在正常范围内的患者106例(18.2%,106/584);APTT在正常上限1~2倍的患者476例(81.5%,476/584);APTT在正常上限2倍以上的患者1例。多重线性回归分析示CCR显著影响达比加群酯谷浓度APTT(P<0.001)。单因素方差分析显示左心房血流不同状态下达比加群酯谷浓度时APTT差异无统计学意义(P=0.535)。结论服用达比加群酯的NVAF患者的达比加群酯谷浓度APTT一般不超过正常上限的2倍。临床上在应用达比加群酯时应格外关注患者肾功能的变化情况。APTT无法准确评估达比加群酯的治疗效果。

Objective To investigate the distribution of the trough activated partial thromboplastin time(APTT)level in patients with nonvalvular atrial fibrillation(NVAF)treated with dabigatran and the associated clinical variables.Furthermore,to explore whether the trough APTT level was different under different status of blood flow in the left atrial.Methods This was a cross-sectional study.NVAF patients treated with dabigatran in Department of Cardiology,The First Affiliated Hospital with Nanjing Medical University were consecutively enrolled from August 2018 to October 2020.All the patients had taken dabigatran regularly for at least three weeks before enrollment.Plasma samples were collected,and APTT levels were measured when the plasma dabigatran concentration was at the trough.Creatinine clearance rate(CCR)was calculated using the Cockcroft-Gault equation.The associated clinical variables of APTT levels were identified using multiple linear regression analysis.The difference in APTT levels under different status of blood flow in the left atrial was analyzed using analysis of variance(ANOVA).Results A total of 584 patients were enrolled.The mean age was(60.3±10.7)years and 397(68.0%,397/584)patients were men.The average CHA_(2)DS_(2)-VASc score and HAS-BLED score of patients was 1.7±1.4 and 1.2±0.9,respectively.A total of 581 patients received dabigatran 110 mg bid,and another 3 patients received dabigatran 150 mg bid.The normal range of APTT in our hospital was 25.0-31.3 s.There were 1 patient with APTT level<25.0 s,106(18.2%,106/584)patients with APTT levels ranging from 25.0 s to 31.3 s,476(81.5%,476/584)patients with APTT levels ranging from 31.4 s to 62.6 s,and 1 patient with APTT level>62.6 s at the trough level of dabigatran.Multiple linear regression analysis revealed that CCR was significantly associated with the trough APTT levels of dabigatran(P<0.001).There was no difference in APTT levels under different status of blood flow in the left atrial(P=0.535).Conclusion The trough-APTT levels of dabigatran in NVAF patients generally did not exceed twice the normal upper limit of 62.6 s.More attention should be paid to the changes of renal function in patients treated with dabigatran.APTT levels cannot accurately reflect the therapeutic effect of dabigatran.