近日，加拿大麦克马斯特大学Remya Giriraju团队比较了接受维持性透析的患者使用螺内酯与安慰剂的疗效。2025年8月16日，《柳叶刀》杂志发表了这一成果。

因肾衰竭而接受维持性透析的患者有很大的心血管发病率和死亡率风险。该研究旨在确定螺内酯是否能减少这些患者的心力衰竭和心血管死亡。

研究组进行了一项国际、平行组、随机对照试验，在12个国家的143个透析项目中进行。患者年龄在45岁及以上，或年龄在18岁及以上且有糖尿病病史，在招募时因肾衰竭接受维持性透析治疗至少3个月。在开放标签试验期间，能够耐受并坚持每天口服25mg螺内酯的患者被随机分配（1:1）继续服用螺内酯或匹配的安慰剂，使用中央计算机块随机化系统（块大小为4）按中心分层。参与者、医疗保健提供者和评估结果的人对小组分配进行了掩饰。主要结局是对所有随机分配的参与者的心血管死亡率或心力衰竭住院时间的综合分析。

在计划对75%的预期主要结局事件进行中期分析后，外部安全性和有效性监测委员会建议因无效而提前停止试验。从2017年9月19日至2024年10月31日，筛选了3689名患者纳入研究，其中3565名患者进入开放标签磨合期，2538名患者随机分配到螺内酯组（n=1260）或安慰剂组（n=1278）。其中女性931人（36.7%），男性1607人（63%）。中位随访时间为1.8年（IQR为0.85 ~ 3.35）。综合主要结局发生在螺内酯组258名参与者（每100患者-年10.46件事件）和安慰剂组276名参与者（每100患者-年11.33件事件）(风险比[HR] 0.92；p = 0·35)。两组间全因死亡相似（死亡率0.95[0.83 - 1.09]），全因住院的死亡率相似（死亡率0.96[0.87 - 1.06]）。

研究结果表明，在接受维持性透析的患者中，与安慰剂相比，每日口服螺内酯25mg并没有降低心血管死亡率和心力衰竭住院率的复合结局。该试验未发现在接受维持性透析的患者中使用螺内酯的益处。未来的研究应考虑替代甾体矿皮质激素受体拮抗剂，以降低接受维持性血液透析患者的心血管发病率和死亡率。

附：英文原文

Title: Spironolactone versus placebo in patients undergoing maintenance dialysis (ACHIEVE): an international, parallel-group, randomised controlled trial

Author: Michael Walsh, David Collister, Martin Gallagher, Patrick B Mark, Janak R de Zoysa, Jessica Tyrwhitt, Karthik Tennankore, Gilmar Reis, Denis Xavier, Wen J Liu, Li Zuo, Amanda Y Wang, Camilo Félix, Laura Sola, Mustafa Arici, Russell Villanueva, Vivekanand Jha, Dalton Précoma, Christian G Rabbat, Sheik Sulthan Alavudeen, Atiya R Faruqui, Mavel López-Flecher, Lonnie Pyne, Ron Wald, Fei Yuan, Kumar Balasubramanian, Shun Fu Lee, Alena Kuptsova, Courtney Christou, P J Devereaux, PJ Devereaux, Michael Walsh, Mustafa Arici, Janak R. de Zoysa, Camilo Félix, Martin Gallagher, Vivekanand Jha, Wen J. Liu, Patrick B. Mark, Gilmar Reis, Laura Sola, Karthik Tennankore, Russell Villanueva, Ron Wald, Amanda Y. Wang, Denis Xavier, Li Zuo, Johannes F.E. Mann, Andrew Smyth, David Collister, Thiago Ferreira, Mats Junek, David Massicotte-Azarniouch, Pavel Roshanov, Emma Wu, Nan Ye, Patrick Parfrey, Stuart Pocock, Marc Pfeffer, Marcello Tonelli, David Jayne, Angela Webster, Sandip Mitra, Akram Al-Gabry, Jessica Tyrwhitt, Courtney Christou, Alena Kuptsova, Kaitlyn McKay, Colin Hardy, Coleen Lapensee, Joanne Wilkinson, Kayla Pohl, Katie Ou-Yang, Heidi Wilton, Kieran Commanda, Matthew Smart, Fei Yuan, John Liu, Shun Fu Less, Peggy Gao, Kumar Balasubramanian, Mark Molec, Emily Dai, Dilani Wijesena, Martin Renters, Nidhi Jethoo, Angela Wang, Yachna Mehta, Victoria Gregory, Jannel Ramos, Jayeeta Chakraborty, Ayesha Malik, Pratiti Ghosh, Hong Man, Sarah Coggan, Rosemary Oliveira, Andrea Mazzetti, Ida Yue, Joe Zhou, Mavel López-Flecher, Akshaya R. Faruqui, Freeda Xavier, Preeti Girish, Remya Giriraju

Issue&Volume: 2025/08/16

Abstract:

Background

Patients undergoing maintenance dialysis for kidney failure are at substantial risk of cardiovascular morbidity and mortality. We aimed to establish if spironolactone reduces heart failure and cardiovascular deaths in these patients.

Methods

ACHIEVE was an international, parallel-group, randomised controlled trial done in 143 dialysis programmes in 12 countries. Patients were aged 45 years or older, or aged 18 years or older with a history of diabetes, and were receiving maintenance dialysis for kidney failure for at least 3 months at the time of recruitment. Patients who were able to tolerate and adhere to spironolactone 25 mg daily orally during an open-label run-in were randomly assigned (1:1) to continue spironolactone or matching placebo, using a central computerised block randomisation system (block sizes of 4) stratified by centre. Participants, health-care providers, and those assessing outcomes were masked to group assignment. The primary outcome was a composite of cardiovascular mortality or hospitalisation for heart failure analysed as time-to-event in all randomly assigned participants. The trial was registered at ClinicalTrials.gov, NCT03020303.

Findings

After a planned interim analysis of 75% of the expected primary outcome events, the external safety and efficacy monitoring committee recommended the trial be stopped early for futility. From Sept 19, 2017, to Oct 31, 2024, 3689 patients were screened for inclusion, 3565 of whom were enrolled in the open-label run-in phase, and 2538 were randomly assigned to spironolactone (n=1260) or placebo (n=1278). 931 (36·7%) participants were female and 1607 (63·3%) were male. Median follow-up was 1·8 years (IQR 0·85–3·35). The composite primary outcome occurred in 258 participants (10·46 events per 100 patient-years) in the spironolactone group and in 276 participants (11·33 per 100 patient-years) in the placebo group (hazard ratio [HR] 0·92 [95% CI 0·78–1·09]; p=0·35). Death from any cause was similar between groups (HR 0·95 [0·83–1·09]) as was hospitalisation for any cause (HR 0·96 [0·87–1·06]).

Interpretation

Among patients receiving maintenance dialysis, spironolactone 25 mg daily orally did not reduce the composite outcome of cardiovascular mortality and hospitalisation due to heart failure compared with placebo. This trial did not identify a benefit of initiating spironolactone in patients receiving maintenance dialysis. Future research should consider alternatives to steroidal mineralocorticoid receptor antagonism to reduce cardiovascular morbidity and mortality in patients receiving maintenance haemodialysis.

DOI: 10.1016/S0140-6736(25)01198-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01198-5/abstract