Université de Lorraine INSERM, Centre, d'Investigations Cliniques Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., K.D., P.R., F.Z.).
Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.).
Circ Heart Fail. 2018 Jul;11(7):e004926. doi: 10.1161/CIRCHEARTFAILURE.118.004926.
Patients with heart failure with reduced ejection fraction have a poor prognosis. The identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual patient. We present an exploratory study of patients enrolled in the EMPHASIS-HF trial (Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms) using latent class analysis with validation using the EPHESUS trial (Eplerenone, a Selective Aldosterone Blocker, in Patients With Left Ventricular Dysfunction After Myocardial Infarction) to identify subgroups of patients with different prognosis and response to eplerenone therapy.
Latent class analysis identifies mutually exclusive groups of individuals maximizing within-group similarities and between-group differences. In the EMPHASIS-HF trial, 2279 heart failure with reduced ejection fraction patients were randomized to eplerenone or placebo and were characterized according to 18 clinical features. Subgroup definitions were applied to 6472 patients enrolled in the EPHESUS trial to validate observations. Event-free survival and effect of eplerenone on the composite of cardiovascular death and heart failure hospitalization were determined for each subgroup. Four subgroups were identified with significant differences in event-free survival (=0.002). The subgroup C had the worst event-free survival in both studies and was characterized by older age, lower body mass index, worse renal function, higher baseline potassium levels, high prevalence of anemia, diabetes mellitus, previous revascularization and higher rates of eplerenone discontinuation, and hyperkalemia during follow-up. Two subgroups (B and C) showed a poorer response to eplerenone in both studies and these groups shared common features such as lower body mass index and high prevalence of anemia. Clinical profiles, prognosis, and treatment response patterns of the 4 subgroups applied in EPHESUS trial presented similarities to those observed in EMPHASIS.
Using a data-driven approach, we identified heart failure with reduced ejection fraction subgroups with significantly different prognoses and potentially different responses to eplerenone. However, these data should be regarded as hypothesis-generating and prospective validation is warranted, to assess the potential clinical implications of these subgroups.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00232180.
射血分数降低的心力衰竭患者预后不良。识别具有不同结局和治疗反应模式的亚组可能有助于为每个个体患者量身定制治疗策略。我们报告了一项使用潜在类别分析对 EMPHASIS-HF 试验（螺内酯治疗射血分数降低的心力衰竭和轻度症状患者）中入组患者进行的探索性研究，并使用 EPHESUS 试验（螺内酯，选择性醛固酮受体阻滞剂，在心肌梗死后左心室功能障碍患者中的应用）进行了验证，以确定对螺内酯治疗有不同预后和反应的患者亚组。
潜在类别分析确定了相互排斥的个体组，这些个体组最大限度地提高了组内相似性和组间差异。在 EMPHASIS-HF 试验中，2279 名射血分数降低的心力衰竭患者被随机分配接受螺内酯或安慰剂，并根据 18 项临床特征进行特征描述。亚组定义应用于 EPHESUS 试验中入组的 6472 名患者，以验证观察结果。确定了每个亚组的无事件生存和螺内酯对心血管死亡和心力衰竭住院复合终点的影响。在两项研究中，有四个亚组在无事件生存方面存在显著差异（=0.002）。亚组 C 在两项研究中的无事件生存最差，其特征为年龄较大、体重指数较低、肾功能较差、基线血钾水平较高、贫血、糖尿病、既往血运重建和螺内酯停药率较高以及随访期间高钾血症发生率较高。两个亚组（B 和 C）在两项研究中对螺内酯的反应均较差，这些亚组具有共同的特征，如体重指数较低和贫血发生率较高。在 EPHESUS 试验中应用的 4 个亚组的临床特征、预后和治疗反应模式与 EMPHASIS 观察到的相似。
使用数据驱动的方法，我们确定了射血分数降低的心力衰竭亚组，这些亚组的预后有显著差异，对螺内酯的反应可能也不同。然而，这些数据应被视为产生假说，需要进行前瞻性验证，以评估这些亚组的潜在临床意义。
