Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study

作     者：Wei Zhou Tao Wang Ling-Juan Zhu Ming-Hua Wen Li-Hua Hu Xiao Huang Chun-Jiao You Ju-Xiang Li Yan-Qing Wu Qing-Hua Wu Hui-Hui Bao Xiao-Shu Cheng 

作者机构：Center for Prevention and Treatment of Cardiovascular Diseases The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330006 China Department of Cardiovascular Medicine The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi 330006 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第18期

页      面：2150-2156页

核心收录：

学科分类：10[医学] 

基　　金：supported by grants from the Major New Drug Creation Program from National Science and Technology Major Project the Science and Technology Planning Project of Jiangxi Province the Key Project of Jiangxi Provincial Education Department 

主　　题：Peripheral leukocyte count Bleeding Nonvalvular atrial fibrillation Threshold effect 

摘      要：Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. Methods: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results: During 6-month follow-up, 87 participants occurred bleeding events. For every 1×10^9/L increase in leukocyte count, the risk of bleeding increased by 11%(hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75×10^9/L. For leukocyte counts 6.75×10^9/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75×10^9/L, the HR (95% CI) was 1.28 (1.09–1.51). Conclusion: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.