Efficacy and Safety of Spironolactone in Acute Heart Failure The ATHENA-HF Randomized Clinical Trial
Efficacy and Safety of Spironolactone in Acute Heart Failure The ATHENA-HF Randomized Clinical Trial
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DOI：
10.1001/jamacardio.2017.2198
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发表时间：
2017-09-01
期刊：
影响因子：
24
通讯作者：
Braunwald, Eugene
中科院分区：
文献类型：
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作者：
Butler, Javed;Anstrom, Kevin J.;Braunwald, Eugene
重要性持续充血与急性心力衰竭（AHF）的不良结局相关。大剂量盐皮质激素受体拮抗剂可缓解充血，克服利尿剂抵抗，减轻AHF患者神经内分泌的不良影响。目的探讨大剂量螺内酯和常规护理对AHF患者N末端B型钠尿肽原的影响（NT-proBNP）水平与单独常规治疗相比。设计，环境，和参与者本双盲和安慰剂在22家美国急性护理医院对既往未接受或接受低剂量治疗的AHF患者进行了一项（或低剂量）对照随机临床试验（每日12.5 mg或25 mg）螺内酯，NT-proBNP水平≥ 1000 pg/mL或B型利钠肽水平≥ 250 pg/mL，干预高剂量螺内酯（100 mg）vs安慰剂或25 mg螺内酯主要结果和指标主要终点是NT-proBNP水平从基线到96小时的变化。次要终点包括临床充血评分、呼吸困难评估、净尿量和净体重变化。安全终点包括高钾血症和肾功能变化。结果共有360名患者被随机分组，其中中位年龄为65岁，其中129名（36%）为女性，200名其中白色占55.5%，黑人占42%，西班牙裔或拉丁裔占2%，（2.5%）为其他人种/种族，左心室射血分数中位数为34%。高剂量螺内酯治疗组的基线中位（四分位距）NT-proBNP水平为4601（2697-9596）pg/mL，常规治疗组为3753（1968-7633）pg/mL。两组之间NT-proBNP降低的对数无显著差异（高剂量螺内酯组为-0.55 [ 95% CI，-0.92至-0.18]，常规治疗组为-0.49 [95% CI，-0.98至-0.14]，P = 0.57）。两组之间的次要终点或30天全因死亡率或心力衰竭住院率均无差异。24、48、72和96小时血清钾和估计肾小球滤过率的变化。结论和相关性在常规护理基础上加用大剂量螺内酯治疗急性心力衰竭患者96小时耐受性良好，但不能改善主要或次要疗效终点。
IMPORTANCE Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high dosesmay relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF.OBJECTIVE To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone.DESIGN, SETTING, AND PARTICIPANTS This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5mg or 25mg daily) spironolactone and had NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more, regardless of ejection fraction.INTERVENTIONS High-dose spironolactone (100mg) vs placebo or 25mg spironolactone (usual care) daily for 96 hoursMAIN OUTCOMES AND MEASURES The primary end pointwas the change in NT-proBNP levels from baseline to 96 hours. Secondary end points included the clinical congestion score, dyspnea assessment, net urine output, and net weight change. Safety end points included hyperkalemia and changes in renal function.RESULTS A total of 360 patients were randomized, of whom the median age was 65 years, 129 (36%) were women, 200 (55.5%) were white, 151 (42%) were black, 8 (2%) were Hispanic or Latino, 9 (2.5%) were of other race/ethnicity, and the median left ventricular ejection fraction was 34%. Baseline median (interquartile range) NT-proBNP levels were 4601 (2697-9596) pg/mL among the group treated with high-dose spironolactone and 3753 (1968-7633) pg/mL among the group who received usual care. There was no significant difference in the log NT-proBNP reduction between the 2 groups (-0.55 [ 95% CI, -0.92 to -0.18] with high-dose spironolactone and -0.49 [95% CI, -0.98 to -0.14] with usual care, P =.57). None of the secondary end point or day-30 all-cause mortality or heart failure hospitalization rate differed between the 2 groups. The changes in serum potassium and estimated glomerular filtration rate at 24, 48, 72, and 96 hours. were similar between the 2 groups.CONCLUSIONS AND RELEVANCE Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary efficacy end points.