Table_1_Safety and Efficacy of Spironolactone in Dialysis-Dependent Patients: Meta-Analysis of Randomized Controlled Trials.DOC

BackgroundPatients with end-stage renal disease (ESRD) are characterized with high risk of heart failure. Although mineralocorticoid receptor antagonists have beneficial effect on relieving cardiac fibrosis and, thus, reduce the incidence of cardiovascular disease and cardiac death, the therapeutic benefits and adverse effects are still controversial. We conducted a meta-analysis to measure the safety and efficacy of spironolactone in patients undergoing dialysis.MethodsA systematic search for randomized controlled trials (RCTs) was performed in PubMed, Embase, and Cochrane databases. Primary outcomes included changes in all-cause mortality (ACM), serum potassium concentration, incidence of hyperkalemia and gynecomastia (GYN). Secondary outcomes included changes in blood pressure (BP), left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Subgroup analysis and sensitivity analysis were further conducted. This research was registered with PROSPERO (International Prospective Register of Systematic Reviews; No. CRD42021287493).ResultsFifteen RCTs with 1,258 patients were enrolled in this pooled-analysis. Spironolactone treatment significantly decreased ACM (RR = 0.42, P < 0.0001), CCV (RR = 0.54, P = 0.008) and LVMI (MD = −6.28, P = 0.002), also increased occurrence of GYN (RR = 4.36, P = 0.0005). However, LVEF (MD = 2.63, P = 0.05), systolic BP (MD = −4.61, P = 0.14) and diastolic BP (MD = −0.12, P = 0.94) did not change between two groups after treatment. Although serum potassium concentration was increased (MD = 0.22, P < 0.0001) after spironolactone supplement, the risk of hyperkalemia remained unchanged (RR = 1.21, P = 0.31). Further subgroup analysis found more obvious advantageous as well as disadvantageous effects in Asian subjects than European or American ones. Also, with more than 9 months of treatment duration, patients achieved more favorable influence than shorter duration.ConclusionsThese results highlight the therapeutic effects of spironolactone on cardiovascular indexes, including ACM, CCV, and LVMI. However, the unignorable increase of GYN incidence and serum potassium level indicate that close monitor in dialysis-dependent patients, especially Asian patients, is essential.

终末期肾病（ESRD）患者常伴有心力衰竭的高风险。尽管利尿剂拮抗剂在缓解心脏纤维化方面具有积极作用，从而降低心血管疾病和心脏病的发病率，但其治疗益处与不良影响仍存在争议。本研究旨在通过荟萃分析评估螺旋内酯在透析患者中的安全性和有效性。方法：在PubMed、Embase和Cochrane数据库中进行了随机对照试验（RCTs）的系统检索。主要结局指标包括全因死亡率（ACM）、血清钾浓度、高钾血症和男性乳腺发育（GYN）的发病率。次要结局指标包括血压（BP）、左心室质量指数（LVMI）和左心室射血分数（LVEF）的变化。进一步进行了亚组分析和敏感性分析。本研究已在PROSPERO（国际前瞻性系统评价注册库；编号CRD42021287493）注册。结果：共纳入15项RCTs，涉及1258名患者。螺旋内酯治疗显著降低了ACM（相对风险 RR = 0.42，P < 0.0001）、冠心病（RR = 0.54，P = 0.008）和LVMI（平均差异 MD = −6.28，P = 0.002），同时GYN的发病率增加（RR = 4.36，P = 0.0005）。然而，治疗后两组间LVEF（MD = 2.63，P = 0.05）、收缩压（MD = −4.61，P = 0.14）和舒张压（MD = −0.12，P = 0.94）没有显著变化。尽管螺旋内酯补充后血清钾浓度升高（MD = 0.22，P < 0.0001），但高钾血症的风险保持不变（RR = 1.21，P = 0.31）。进一步的亚组分析发现，与欧洲或美国患者相比，亚洲患者显示出更为显著的益处及不利影响。此外，治疗持续时间超过9个月的患者，其效果优于治疗时间较短的患者。结论：这些结果突出了螺旋内酯对心血管指标，包括ACM、冠心病和LVMI的治疗效果。然而，GYN发病率和血清钾水平的不容忽视的升高提示，在依赖透析的患者中，尤其是亚洲患者，密切监测至关重要。