Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial
Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial
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DOI：
10.1093/eurjhf/hfp136
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发表时间：
2009-11-01
影响因子：
18.2
通讯作者：
Zannad, Faiez
中科院分区：
文献类型：
--
作者：
Adamopoulos, Chris;Ahmed, Ali;Zannad, Faiez
为了验证左心室收缩功能障碍 (LVSD) 和心力衰竭 (HF) 患者早期急性心肌梗死 (AMI) 后开始依普利农与更好的长期结局相关的假设。 EPHESUS 研究的 6632 名患者在 AMI 指数发生后第 3 天至 14 天（中位 = 7 天）被随机分配，其中 3319 名患者被分配到依普利农。我们根据开始治疗的中位时间（< 7 天-“较早”，>= 7 天-“较晚”）分析了依普利酮开始治疗时间与安慰剂的差异效应。使用 Cox 比例风险回归分析，在平均 16 个月的随访中评估对结果的影响。与“早期”安慰剂相比，较早开始服用依普利酮（< 7 天）可将全因死亡风险降低 31%（P = 0.001），并将心血管 (CV) 住院/心血管死亡风险降低 24% (P < 0.0001)，将心源性猝死 (SCD) 风险降低 34% (P < 0.0001)。相比之下，较晚开始依普利农（>=7天）对结果没有显着影响。随机化时间和治疗之间的相互作用显着。在多变量模型中进行风险调整后，这些关联基本保持不变。AMI 后早期服用依普利农（3-7 天）可改善 LVSD 和 HF 患者的预后。当依普利农稍后（> = 7天）开始使用时，没有观察到这种益处。
To test the hypothesis that an earlier post-acute myocardial infarction (AMI) eplerenone initiation in patients with left ventricular systolic dysfunction (LVSD) and heart failure (HF) is associated with better long-term outcomes.The 6632 patients of the EPHESUS study were randomized from day 3 to 14 after the index AMI (median = 7 days), of these 3319 were assigned to eplerenone. We analysed the differential effects of time-to-eplerenone initiation vs. placebo, based on the median time to initiation of treatment (< 7 days-'earlier', >= 7days-'later'). Effects on outcomes were evaluated over a mean 16-month follow-up, using Cox proportional hazards regression analysis. The earlier eplerenone initiation (< 7 days) reduced the risk of all-cause mortality by 31% (P = 0.001) when compared with the 'earlier' placebo' and also reduced the risks of cardiovascular (CV) hospitalization/CV mortality by 24% (P < 0.0001) and sudden cardiac death (SCD) by 34% (P < 0.0001). In contrast, later eplerenone initiation (>= 7 days) had no significant effect on outcomes. Interactions between time-to-randomization and treatment were significant. These associations remained substantially unchanged after risk adjustment in multivariable models.An earlier eplerenone administration (3-7days) post-AMI improved outcomes in patients with LVSD and HF. This benefit was not observed when eplerenone was initiated later (>= 7days).