Université de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.
Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.
Eur J Heart Fail. 2023 Aug;25(8):1444-1449. doi: 10.1002/ejhf.2952. Epub 2023 Jul 7.
Eplerenone reduces the risk of cardiovascular death or first hospitalization for heart failure (HF) in patients with HF and a reduced ejection fraction (HFrEF), but it is still frequently underused in routine practice. We evaluated the time course of benefits of eplerenone after its initiation in HFrEF patients from the EMPHASIS-HF trial.
The EMPHASIS-HF trial was a double-blind randomized clinical trial assessing the effect of eplerenone in patients (n = 2737, mean age 68.6 ± 7.6 years, 22.3% women) with HFrEF and mild symptoms. The time trajectories for the effect of eplerenone versus placebo on the primary composite endpoint (cardiovascular death or first hospitalization for HF) were investigated using Cox proportional hazards models with truncated data at each day post-randomization. A significant reduction in the primary composite endpoint was observed 26 days after randomization (hazard ratio 0.58; 95% confidence interval, 0.34-1.00, p = 0.049). Eplerenone was first associated with a significant reduction in the primary endpoint in 35 days or less in most subgroups, including patients with HF history ≥18 months (day 24), estimated glomerular filtration rate <60 ml/min (day 12), ischaemic HF aetiology (day 28), age ≥65 years (day 28), narrow QRS (day 30), higher MAGGIC score (day 35), lower potassium (day 30), left ventricular ejection fraction ≥30% (day 28) or already treated with beta-blockers (day 25).
Eplerenone provides statistically significant and clinically meaningful benefits shortly after treatment initiation in most patients, irrespective of clinical profile. This result reinforces the need for an early initiation of eplerenone in HFrEF, as part of rapidly instituting guideline-directed medical therapy.
依普利酮可降低射血分数降低的心力衰竭（HFrEF）患者的心血管死亡或因心力衰竭首次住院的风险，但在常规实践中仍未得到充分应用。我们评估了 EMPHASIS-HF 试验中 HFrEF 患者开始依普利酮治疗后获益的时间过程。
EMPHASIS-HF 试验是一项双盲随机临床试验，评估了依普利酮对 2737 例 HFrEF 患者（平均年龄 68.6±7.6 岁，22.3%为女性）的疗效。使用 Cox 比例风险模型，根据随机后每天的截断数据，研究依普利酮与安慰剂对主要复合终点（心血管死亡或因心力衰竭首次住院）的影响。与安慰剂相比，随机后 26 天主要复合终点显著降低（风险比 0.58；95%置信区间，0.34-1.00，p=0.049）。大多数亚组，包括心力衰竭史≥18 个月（第 24 天）、估计肾小球滤过率<60ml/min（第 12 天）、缺血性心力衰竭病因（第 28 天）、年龄≥65 岁（第 28 天）、QRS 波群变窄（第 30 天）、MAGGIC 评分较高（第 35 天）、血钾较低（第 30 天）、左心室射血分数≥30%（第 28 天）或已接受β受体阻滞剂治疗（第 25 天），依普利酮在 35 天或更短时间内首次与主要终点的显著降低相关。
在大多数患者中，依普利酮在治疗开始后不久即可提供具有统计学意义和临床意义的获益，无论其临床特征如何。这一结果强化了依普利酮在 HFrEF 中的早期应用，这是迅速实施指南导向的医学治疗的一部分。
