Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium.
Department of Medicine and Life Sciences, University Hasselt, Hasselt, Belgium.
Clin Res Cardiol. 2022 Apr;111(4):380-392. doi: 10.1007/s00392-021-01853-8. Epub 2021 Apr 23.
Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF.
The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135 mmol/L or > 145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization.
A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect.
Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF.
ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.
钠变化在伴有左心室收缩功能障碍（LVSD）和/或心力衰竭（HF）的心肌梗死（MI）中很常见。钠在远曲小管中被精细调节，依普利酮在其中表现出一些多效性作用。关于依普利酮对血清钠的影响以及在伴有 LVSD 和/或 HF 的 MI 患者中钠变化的预后相关性，人们知之甚少。
EPHESUS 试验将 6632 名患者随机分配至依普利酮或安慰剂组。低钠血症和高钠血症的定义分别为血清钠<135mmol/L 和>145mmol/L。线性混合模型和时间更新的 Cox 回归分析分别用于确定依普利酮对钠变化的影响和钠变化的预后重要性。主要结局是全因死亡率和心血管（CV）死亡率和 CV 住院的复合结局。
共有 6221 名患者在基线后进行了钠测量，797 名患者发生低钠血症（平均每例患者发生 0.2 次事件），1476 名患者发生高钠血症（平均每例患者发生 0.4 次事件）。接受依普利酮治疗的患者在随访期间的平均血清钠水平较低（140 与 141mmol/L；p<0.0001），低钠血症发作的发生率更高（15%与 11%；p=0.0001），高钠血症发作的发生率更低（22%与 26%；p=0.0003）。低钠血症与安慰剂组所有结局终点的不良预后相关，但高钠血症与安慰剂组和依普利酮组的所有结局终点均不相关（交互 p 值均<0.05）。基线钠值不影响依普利酮降低各种终点的治疗效果（交互 p 值均>0.05）。依普利酮治疗后新发低钠血症并不会降低依普利酮的治疗效果。
依普利酮可使血清钠略有降低。依普利酮的有益作用不受基线血清钠或低钠血症的影响。钠变化不应阻止临床医生为伴有 LVSD 和/或 HF 的 MI 患者开具依普利酮。
ClinicalTrials.gov 标识符：NCT00232180。血清钠和依普利酮在伴有左心室功能障碍或心力衰竭的心肌梗死患者中的应用：EPHESUS 试验的见解。
