螺内酯治疗射血分数保留的心力衰竭。

Spironolactone for heart failure with preserved ejection fraction.

机构信息

From the University of Michigan School of Medicine, Ann Arbor (B.P.); the Cardiovascular Division, Brigham and Women's Hospital, Boston (M.A.P., B.C., A.S.D., E.F.L., S.D.S.); New England Research Institutes, Watertown, MA (S.F.A., B.H., C.T.K., S.M.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.B., J.L.F., S.Y.); Veterans Affairs Medical Center and University of Minnesota, Minneapolis (I.S.A.); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (N.C.); Estudios Clinicos Latinoamerica, Rosario, Argentina (R.D.); Pirogov Russian National Research Medical University, Moscow (I.G.); New York Methodist Hospital, Brooklyn (J.F.H.); Montreal Heart Institute, Montreal (E.O.); University of Washington Medical Center, Seattle (J.L.P.); Diagnostic Services Clinic, Tbilisi, Georgia (T.S.); Northwestern University, Chicago (S.J.S.); and the University of Wisconsin, Madison (N.K.S.).

出版信息

N Engl J Med. 2014 Apr 10;370(15):1383-92. doi: 10.1056/NEJMoa1313731.

DOI:10.1056/NEJMoa1313731

PMID:24716680

Abstract

BACKGROUND

Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction.

METHODS

In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure.

RESULTS

With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis.

CONCLUSIONS

In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

摘要

背景

醛固酮受体拮抗剂可改善射血分数降低的心力衰竭患者的预后。我们评估了螺内酯在射血分数保留的心力衰竭患者中的作用。

方法

在这项随机、双盲试验中，我们将 3445 例有症状的心力衰竭且左心室射血分数≥45%的患者随机分为螺内酯（每天 15 至 45 毫克）或安慰剂组。主要终点是心血管原因死亡、心搏骤停未遂或心力衰竭住院治疗的复合终点。

结果

平均随访 3.3 年后，螺内酯组 1722 例患者中有 320 例（18.6%），安慰剂组 1723 例患者中有 351 例（20.4%）发生主要终点事件（风险比，0.89；95%置信区间[CI]，0.77 至 1.04；P=0.14）。主要终点的组成部分中，只有心力衰竭住院的发生率在螺内酯组低于安慰剂组（螺内酯组 206 例[12.0%]，安慰剂组 245 例[14.2%]；风险比，0.83；95%CI，0.69 至 0.99，P=0.04）。螺内酯治疗并未显著降低总死亡率或因任何原因住院的发生率。螺内酯治疗与血清肌酐水平升高和高钾血症发生率增加一倍（18.7%，安慰剂组为 9.1%）相关，但低钾血症减少。频繁监测时，严重不良事件的发生率、血清肌酐水平为 3.0 mg/dL（265 μmol/L）或更高或透析的发生率无显著差异。