Eur Heart J：临床研究发现服用地高辛患者的死亡率增加

地高辛广泛用于房颤的控制。然而，地高辛与死亡率增加有关。是否地高辛本身的毒副作用还是用药者体质弱并且有合并症导致死亡率增加，尚不清楚。近期，美国的吉尔心脏研究所肯塔基大学的一项研究表明地高辛与房颤病人的死亡率增加密切相关，该结果发表在《欧洲心脏杂志》上。

该研究应用多元Cox比例风险模型评估了节律管理会随访调查的房颤病人死亡率与地高辛的关系。研究分析了心衰患者或非心衰患者及所有亚群，心衰定义为有心衰史或/并射血分数小于40%。地高辛与所有原因导致的死亡率（估计风险比1.41，95%可信区间1.19-1.67，P<0.001）、心血管死亡率（估计风险比1.35，95%可信区间1.06-1.71，P=0.016）和心律失常死亡率（估计风险比1.61，95%可信区间1.12-2.30，P=0.009）。不管病人是否存在心衰，地高辛与所有原因导致的死亡率增加相关（估计风险比1.37，95%可信区间1.05-1.79，P=0.019；估计风险比1.41，95%可信区间1.09-1.84，P=0.010）。地高辛与性别的关系对所有原因导致的死亡率或心血管疾病死亡率没统计学意义。

总结结果得出如下结论：房颤病人在临床症状和合并症纠正后，不论性别或是否存在心衰，地高辛与所有原因导致的死亡率、心血管疾病死亡率和心律失常导致的死亡率增加相关。这项研究提示临床应用地高辛治疗房颤病人时，要对地高辛的安全性重新评估。 

Increased mortality among patients taking digoxin—analysis from the AFFIRM study
Aims
Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF.
Methods and results
The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19–1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06–1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12–2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05–1.79, P = 0.019 and EHR 1.41, 95% CI 1.09–1.84, P = 0.010, respectively). There was no significant digoxin–gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality.
Conclusion
Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.