Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial
Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial
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DOI：
10.1016/j.kint.2018.08.034
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发表时间：
2019-04-01
影响因子：
19.6
通讯作者：
Kusek, John
中科院分区：
文献类型：
--
作者：
Charytan, David M.;Himmelfarb, Jonathan;Kusek, John
螺内酯治疗终末期肾病的安全性和有效性尚不确定。在一项双盲、安慰剂对照、多剂量试验中，我们将129名维持性血液透析患者随机分为安慰剂（n = 51）、螺内酯12.5 mg （n = 27）、25 mg （n = 26）或50 mg (n = 25)，持续36周，以评估其安全性、耐受性和可行性，并探讨心血管疗效。主要安全终点是高钾血症（6.5 mEq/L）和低血压，需要急诊或住院。采用多普勒超声心动图评估舒张功能。125名参与者（97%）完成了剂量递增，两组之间永久停药的情况无显著差异（安慰剂组27.5%，联合螺内酯组16.7%，50 mg组28%）。原发性低血压的结果并不常见，与螺内酯和安慰剂相似（0.11 vs 0事件/患者年）。男性乳房发育罕见，组间无显著差异。舒张功能的改变与螺内酯和安慰剂相似。在这项小型研究中，螺内酯在仔细监测的维持性血液透析患者中似乎是安全的，但不影响心血管参数。当剂量增加到每天50毫克时，高钾血症更频繁发生。
The safety and efficacy of spironolactone is uncertain in end-stage renal disease. We randomized 129 maintenance hemodialysis patients to placebo (n = 51) or spironolactone 12.5 mg (n = 27), 25 mg (n = 26), or 50 mg (n = 25) daily for 36 weeks in a double-blind, placebo-controlled, multiple dosage trial to assess safety, tolerability and feasibility and to explore cardiovascular efficacy. The primary safety endpoints were hyperkalemia (potassium > 6.5 mEq/L) and hypotension requiring emergency department visit or hospitalization. Diastolic function was assessed by Doppler echocardiography. 125 participants (97%) completed dose escalation, with no significant difference in permanent study drug discontinuation between the groups (27.5% in placebo versus 16.7% in the combined spironolactone groups and 28% in the 50 mg group). Hyperkalemia frequency was similar between spironolactone and placebo (0.49 versus 0.50 events per patient-year) but demonstrated a significant linear trend due primarily to an increased event rate at the 50 mg dose (0.89 events per patient-year). The primary hypotension outcome was infrequent and similar with spironolactone and placebo (0.11 versus 0 events per patient-year). Gynecomastia was rare and did not differ significantly between groups. Change in diastolic function was similar with spironolactone and placebo. Spironolactone appears safe in carefully monitored maintenance hemodialysis patients, but did not affect cardiovascular parameters in this small study. Hyperkalemia occurs more frequently as dosage increases to 50 mg daily.