Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation
Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation
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DOI：
10.1056/nejmoa0803778
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发表时间：
2009-02-12
影响因子：
158.5
通讯作者：
Connolly, Stuart J.
中科院分区：
文献类型：
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作者：
Hohnloser, Stefan H.;Crijns, Harry J. G. M.;Connolly, Stuart J.
背景决奈达隆是一种新的抗心律失常药物，正在开发用于治疗房颤患者。方法我们进行了一项多中心试验，以评估决奈达隆在4628例有其他死亡危险因素的房颤患者中的使用。患者被随机分配接受决奈达隆（400 mg，每日两次）或安慰剂。主要结局为首次因心血管事件住院或死亡。结果平均随访时间为21 ± 5个月，2301例患者中有696例提前停药（30.2%）接受决奈达隆治疗的患者和716/2327例接受安慰剂治疗的患者（30.8%），主要是由于不良事件。决奈达隆组734例患者（31.9%）和安慰剂组917例患者（39.4%）发生主要结局，决奈达隆的风险比为0.76（95%置信区间[ CI]，0.69至0.84; P< 0.001）。决奈达隆组有116例死亡（5.0%），安慰剂组有139例死亡（6.0%）（风险比，0.84; 95% CI，0.66 - 1.08; P = 0.18）。决奈达隆组有63例（2.7%）心血管原因死亡，安慰剂组有90例（3.9%）（风险比，0.71; 95% CI，0.51 - 0.98; P = 0.03），主要是由于决奈达隆心律失常死亡率降低。决奈达隆组心动过缓、QT间期延长、恶心、腹泻、皮疹和血清肌酐水平升高的发生率高于安慰剂组。甲状腺和肺部相关不良事件的发生率在两组之间无显著差异。结论屈洛酮降低了房颤患者因心血管事件住院或死亡的发生率。（临床试验。政府编号，NCT 00174785）。
Background Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation.Methods We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death. Patients were randomly assigned to receive dronedarone, 400 mg twice a day, or placebo. The primary outcome was the first hospitalization due to cardiovascular events or death. Secondary outcomes were death from any cause, death from cardiovascular causes, and hospitalization due to cardiovascular events.Results The mean follow- up period was 21 +/- 5 months, with the study drug discontinued prematurely in 696 of the 2301 patients ( 30.2%) receiving dronedarone and in 716 of the 2327 patients ( 30.8%) receiving placebo, mostly because of adverse events. The primary outcome occurred in 734 patients ( 31.9%) in the dronedarone group and in 917 patients ( 39.4%) in the placebo group, with a hazard ratio for dronedarone of 0.76 ( 95% confidence interval [ CI], 0.69 to 0.84; P< 0.001). There were 116 deaths ( 5.0%) in the dronedarone group and 139 ( 6.0%) in the placebo group ( hazard ratio, 0.84; 95% CI, 0.66 to 1.08; P = 0.18). There were 63 deaths from cardiovascular causes ( 2.7%) in the dronedarone group and 90 ( 3.9%) in the placebo group ( hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = 0.03), largely due to a reduction in the rate of death from arrhythmia with dronedarone. The dronedarone group had higher rates of bradycardia, QT- interval prolongation, nausea, diarrhea, rash, and an increased serum creatinine level than the placebo group. Rates of thyroid- and pulmonary- related adverse events were not significantly different between the two groups.Conclusion Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation. (ClinicalTrials. gov number, NCT00174785.).