[Association between duration of digoxin use and adverse outcomes among Chinese patients with atrial fibrillation]

Objective: We aimed to explore the impact of digoxin use on outcomes in Chinese patients with atrial fibrillation (AF). Methods: We used the dataset from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study. According to the inclusion and exclusion criteria, 10 472 eligible patients enrolled from August 2011 to December 2016 were included in this ancillary study. The patients were classified into three groups according to the status of digoxin use at study enrollment, patients already receiving digoxin before registry were represented as continuous group, patients initiated on digoxin for the first time were represented as newly group, and patients without digoxin prescription at enrollment were represented as control group. Patients were followed by telephone or outpatient service every 6 months. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to investigate the association of digoxin use with adverse outcomes (all-cause death, cardiovascular death and cardiovascular hospitalization). Results: In the overall study population, men accounted for 42.8%, and the average age was (66.9±11.8) years. There were 777（7.42%）patients in continuous group, 375 (3.58%) patients in newly group, and 9 320 (89.00%) patients in control group. Compared with the control group, the patients in the newly group and the continuous group were older, had faster heart rate, lower estimated glomerular filtration rate, higher proportion of persistent atrial fibrillation, heart failure, renal insufficiency, diabetes mellitus, ischemic stroke, coronary heart disease, vascular disease and bleeding history. At the same time, the patients in the newly group and the continuous group were treated more often with anticoagulants, antiplatelet drugs, ACE inhibitors or angiotensin receptor blockers, beta-receptor blockers while the proportion of antiarrhythmic drugs was lower as compared to control group (P<0.05). During a median follow-up of 36 months (interquartile range: 18-48 month), risk of all-cause mortality was significantly higher in newly group compared to control group (7.3% vs. 4.7%, P<0.05), the rates of all-cause mortality, cardiovascular death and cardiovascular hospitalization were all higher in continuous group than in control group (8.0% vs. 4.7%; 4.7% vs. 3.0%; 16.7% vs. 11.8%; P all<0.05). After adjustment for age, male, body mass index, blood pressure, heart rate, renal function, AF type, history of stroke, heart failure, diabetes, coronary artery disease and other drugs treatment, the association between newly group and adverse outcomes was not significant, however, digoxin use was associated with increased all-cause mortality (HR 1.26; 95%CI 1.04-1.56; P=0.019), cardiovascular death (HR 1.38; 95%CI 1.08-1.77, P =0.01), and cardiovascular hospitalization (HR 1.10; 95%CI 1.06-1.52, P=0.02) in continuous group. Conclusion: Continuous digoxin use is associated with a significant increase in adverse outcomes among Chinese patients with atrial fibrillation.

目的： 评估中国心房颤动（房颤）患者地高辛应用时限与不良预后的相关性。 方法： 本研究数据来自多中心、前瞻性中国房颤注册队列。根据纳入及排除标准，2011年8月至2016年12月招募的患者中共有10 472例纳入本研究。根据入组时地高辛应用情况分为持续组（入组前已开始应用地高辛），新进组（入组时首次应用地高辛）和对照组（入组时未应用地高辛）。患者入组后每6个月对其进行门诊或电话随访，终点事件包括全因死亡、心血管死亡和心血管疾病住院。采用Kaplan-Meier生存分析和Cox回归分析不同地高辛应用时限与终点事件之间的相关性。 结果： 纳入的10 472患者中，年龄（66.9±11.8）岁，男性4 481例（42.79%）。其中持续组777例（7.42%），新进组375例（3.58%），对照组9 320例（89.00%）。与对照组比较，新进组和持续组患者年龄更大，心率更快，估计肾小球滤过率更低，持续性房颤比例更高，合并心力衰竭、肾功能不全、糖尿病、缺血性脑卒中、冠心病、血管疾病、出血史的比例更高，同时应用抗血小板药物、血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂、β受体阻滞剂比例更高，应用抗心律失常药物比例更低（P均<0.05）。与新进组相比，持续组患者年龄、性别差异无统计学意义，收缩压更低，心率更慢，持续性房颤比例更高，合并心力衰竭比例更低，高脂血症比例更高，同时应用口服抗凝药比例更高，抗血小板药物、血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂、抗心律失常药物比例更低（P均<0.05）。中位随访36（18，48）个月，生存分析显示新进组年化全因死亡率高于对照组（7.3%比4.7%，P<0.05），而持续组年化全因死亡、心血管死亡和住院率均高于对照组（8.0%比4.7%，4.7%比3.0%，16.7%比11.8%；P均<0.05）。Cox多因素分析结果显示相比对照组，新进组与不良预后的相关性差异无统计学意义；而持续组与全因死亡（HR=1.26，95%CI：1.04~1.56，P=0.019）、心血管事件死亡（HR=1.38，95%CI：1.08~1.77，P=0.01）和心血管住院（HR=1.38，95%CI：1.08~1.77，P=0.01）事件的增加独立相关。 结论： 中国房颤患者持续应用地高辛可能与不良预后增加相关。.

Keywords: Adverse outcomes; Atrial fibrillation; Digoxin.