University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
Duke University Medical Center, Duke University School of Medicine, Durham, North Carolina.
Am J Cardiol. 2019 Jan 1;123(1):69-74. doi: 10.1016/j.amjcard.2018.09.036. Epub 2018 Oct 4.
In 2015, 3 independent meta-analyses raised concerns about digoxin therapy being associated with an increased mortality risk in patients with atrial fibrillation (AF) and with heart failure (HF). Although several other studies have been published since then fostering these safety issues, the most recent 2016 European guidelines for AF still recommend this therapy as a class I indication. We performed an updated systematic review and random-effect meta-analysis on publications up to March 2018 reporting data on digoxin associated mortality in subjects with AF or HF. Based on the adjusted survival data of all identified 37 trials comprising a total of 825,061 patients, digoxin use was associated with an increased relative risk of all-cause mortality (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 to 1.29, p <0.01). Treatment with digoxin was associated with an increased mortality risk in the subgroup of patients with AF (n = 627,620, HR 1.23, 95% CI, 1.17 to 1.30, p <0.01), and in the subgroup of patients with HF (n = 197,441, HR 1.11, 95% CI, 1.06 to 1.16, p<0.01). A sensitivity analysis of studies reporting data on new digoxin users (n = 41,687) demonstrated an even higher risk for all-cause mortality compared with patients not receiving cardiac glycosides (HR 1.47, 95% CI, 1.15 to 1.88, p <0.01). In conclusion, this updated meta-analysis confirms that digoxin use is associated with increased mortality in patients with AF or HF.
2015 年，3 项独立的荟萃分析引起了人们对地高辛治疗与心房颤动（AF）和心力衰竭（HF）患者死亡率增加相关的担忧。尽管此后发表了其他几项研究来支持这些安全性问题，但最近 2016 年的 AF 欧洲指南仍将该治疗推荐为 I 类适应证。我们对截至 2018 年 3 月的发表文献进行了更新的系统评价和随机效应荟萃分析，报告了 AF 或 HF 患者中与地高辛相关的死亡率数据。基于所有 37 项试验（共包括 825061 名患者）的调整生存数据，地高辛的使用与全因死亡率的相对风险增加相关（风险比[HR]1.17，95%置信区间[CI]1.05 至 1.29，p<0.01）。在 AF 患者亚组（n=627620，HR 1.23，95%CI，1.17 至 1.30，p<0.01）和 HF 患者亚组（n=197441，HR 1.11，95%CI，1.06 至 1.16，p<0.01）中，地高辛治疗与死亡率风险增加相关。对报告新使用地高辛患者数据的研究（n=41687）进行敏感性分析表明，与未使用强心苷的患者相比，全因死亡率的风险更高（HR 1.47，95%CI，1.15 至 1.88，p<0.01）。总之，本更新的荟萃分析证实，地高辛的使用与 AF 或 HF 患者的死亡率增加相关。
