Inserm CIC Plurithématique 1433, UMRS 1116 Inserm, CHRU Nancy, Vandoeuvre-lès-Nancy, France.
Cardiovascular Department, CHRU Nancy, Vandoeuvre-lès-Nancy, France.
Eur J Heart Fail. 2017 Sep;19(9):1186-1197. doi: 10.1002/ejhf.792. Epub 2017 Mar 16.
An excessive production of aldosterone influences outcome in patients with heart failure (HF) and in obese patients. Findings from laboratory studies suggest that chronic aldosterone blockade maybe more beneficial in abdominally obese HF-prone rats. In the current study, we investigated if the clinical response to a mineralocorticoid receptor antagonist in mildly symptomatic HF patients varied by abdominal obesity.
A total of 2587 NYHA class II, reduced ejection fraction HF (HFrEF) patients enrolled in the EMPHASIS-HF trial were randomly assigned to eplerenone and placebo. In this post hoc analysis, patients were categorized according to waist circumference (WC) (normal if WC < 102 cm in men and < 88 cm in women; abdominal obesity if WC ≥ 102 cm in men and ≥ 88 cm women). The potential statistical interaction between the treatment and WC was assessed on the primary endpoint of death from cardiovascular causes or hospitalization for HF and other secondary endpoints. Over a median follow-up of 21 months, a significant benefit of eplerenone for the primary outcome was noted in both normal [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98, P = 0.03] and increased (HR 0.48, 95% CI 0.37-0.63, P < 0.0001) WC subgroups, but the latter patients appeared to receive greater benefit than patients with normal WC (P for interaction = 0.01). This suggests a significant quantitative (treatment effect varies in magnitude by subgroup, but is always in same direction) rather than a qualitative interaction (direction of the treatment effect varies by subgroup) between eplerenone and WC in the adjusted analysis. Mean doses of eplerenone, blood pressure and serum potassium changes and adverse events were similar between WC subgroups.
In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.
醛固酮的过度产生会影响心力衰竭（HF）患者和肥胖患者的预后。实验室研究结果表明，慢性醛固酮阻断在易患 HF 的腹部肥胖大鼠中可能更有益。在本研究中，我们研究了在轻度有症状的 HF 患者中，对盐皮质激素受体拮抗剂的临床反应是否因腹部肥胖而有所不同。
共有 2587 名 NYHA Ⅱ级、射血分数降低的 HF（HFrEF）患者参加了 EMPHASIS-HF 试验，他们被随机分配接受依普利酮和安慰剂。在本事后分析中，根据腰围（WC）（男性 WC<102cm，女性 WC<88cm 为正常；男性 WC≥102cm，女性 WC≥88cm 为腹部肥胖）对患者进行分类。评估了治疗与 WC 之间潜在的统计学相互作用，主要终点是心血管原因导致的死亡或 HF 住院，以及其他次要终点。中位随访 21 个月后，在正常 WC[风险比（HR）0.77，95%置信区间（CI）0.61-0.98，P=0.03]和增加的 WC（HR 0.48，95%CI 0.37-0.63，P<0.0001）亚组中，依普利酮对主要结局均有显著获益，但后者患者的获益似乎大于正常 WC 患者（P 交互=0.01）。这表明在调整分析中，依普利酮与 WC 之间存在显著的定量（亚组间治疗效果的大小不同，但始终朝同一方向）而非定性（亚组间治疗效果的方向不同）相互作用。依普利酮、血压和血清钾变化以及不良事件的平均剂量在 WC 亚组之间相似。
在 EMPHASIS-HF 中，依普利酮改善了有和没有腹部肥胖的 HFrEF 患者的预后，尽管在腹部肥胖患者中获益似乎更为明显。这些发现可能具有假设生成的潜力，需要在其他 HFrEF 人群中得到复制。
