Eisen Alon, Ruff Christian T, Braunwald Eugene, Hamershock Rose A, Lewis Basil S, Hassager Christian, Chao Tze-Fan, Le Heuzey Jean Yves, Mercuri Michele, Rutman Howard, Antman Elliott M, Giugliano Robert P
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.
Department of Medicine, Harvard Medical School, Boston, MA.
J Am Heart Assoc. 2017 Jun 30;6(7):e006035. doi: 10.1161/JAHA.117.006035.
Digoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF).
In the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow-up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10-2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36-2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all-cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (<0.01 for each), but not with noncardiovascular death, stroke/systemic embolism, or myocardial infarction.
In this observational analysis of patients with atrial fibrillation without investigator-reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.
尽管缺乏随机对照试验，但地高辛仍广泛应用于房颤患者。观察性研究报告了其与死亡率之间相互矛盾的结果，这可能是由于心力衰竭（HF）的存在导致的残余混杂因素所致。
在ENGAGE AF-TIMI 48（房颤患者应用新一代Xa因子有效抗凝-心肌梗死溶栓48）试验中，通过对房颤患者在中位随访2.8年期间基线使用地高辛的情况，研究了有或无HF患者的临床结局。HF在基线时定义为既往或当前临床C期或D期HF。在纳入的21105例患者中，6327例（30%）在基线时接受了地高辛治疗。在无HF的患者（n = 8981）中，使用地高辛（20%）与心源性猝死独立相关（校正风险比，1.51；95%CI，1.10 - 2.08），年龄、性别、左心室射血分数、肾功能或合并用药均无显著交互作用（每项均>0.05）。倾向匹配分析得到了一致的结果（心源性猝死校正风险比，1.90；95%CI，1.36 - 2.65）。在有HF的患者（n = 12124）中，使用地高辛（37%）与全因死亡、心血管死亡、心源性猝死以及HF/心源性休克导致的死亡增加相关（每项均<0.01），但与非心血管死亡、卒中/全身性栓塞或心肌梗死无关。
在这项对无研究者报告HF的房颤患者的观察性分析中，使用地高辛与心源性猝死显著相关。虽然不能排除残余混杂因素，但地高辛使用与更差临床结局之间的关联凸显了在随机试验中研究地高辛使用情况的必要性，尤其是在为房颤患者控制心率而开具地高辛处方时。
