Okin Peter M, Hille Darcy A, Wachtell Kristian, Kjeldsen Sverre E, Boman Kurt, Dahlöf Björn, Devereux Richard B
aGreenberg Division of Cardiology, Weill Cornell Medical College, New York bMerck Research Laboratories, West Point, Pennsylvania, USA cDepartment of Medicine, Glostrup University Hospital, Glostrup, Denmark dDepartment of Cardiology, University of Oslo, Ullevål Hospital, Oslo, Norway eResearch Unit, Department of Medicine, Skellefteå Hospital Institution of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden fDepartment of Medicine, Sahlgrenska University Hospital/Östra, Göteborg, Sweden.
J Hypertens. 2015 Jul;33(7):1480-6. doi: 10.1097/HJH.0000000000000559.
Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined.
All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18-2.19, P = 0.003). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow-Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73-1.48, P = 0.839).
In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies.
地高辛广泛用于控制房颤的心率。然而，最近的研究报告了地高辛用于房颤患者时与死亡率之间的关联存在相互矛盾的结果。此外，地高辛使用与高血压合并房颤患者死亡率之间的关系尚未得到研究。
在氯沙坦干预降低高血压终点事件（LIFE）试验的一项子研究的事后分析中，对937例高血压患者的全因死亡率与治疗期间使用地高辛的情况进行了研究，这些患者在基线时心电图显示左心室肥厚且合并房颤（n = 134）或在随访期间发生房颤（n = 803），随机分配接受氯沙坦或阿替洛尔治疗。在平均4.7±1.1年的随访期间，167例患者死亡（17.8%），372例（39.7%）接受了地高辛治疗。在单因素Cox分析中，将治疗期间使用地高辛作为时变协变量纳入分析，结果显示使用地高辛的患者死亡风险高61%（风险比1.61，95%置信区间1.18 - 2.19，P = 0.003）。在对该人群中其他单因素死亡预测因素进行调整后，包括年龄、糖尿病史、缺血性心脏病史、中风史或心力衰竭史、基线康奈尔乘积、QRS时限、心率、血糖、肌酐和高密度脂蛋白胆固醇，以及将使用地高辛的倾向评分作为标准协变量纳入分析，并将治疗期间的心率、脉压和索科洛夫 - 里昂电压作为时变协变量进行调整后，地高辛使用不再是死亡率的显著预测因素（风险比1.04，95%置信区间0.73 - 1.48，P = 0.839）。
在心电图显示左心室肥厚且合并现有或新发房颤的高血压患者中，在对其他独立死亡预测因素以及该人群中与使用地高辛倾向相关的因素进行调整后，使用地高辛与全因死亡率显著增加无关。这些发现表明在一些研究中，除了地高辛使用外，其他因素可能导致了使用地高辛时死亡率增加。
