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螺内酯可改善合并慢性肾脏病的急性心肌梗死患者的全因死亡率和再住院率。

Spironolactone Improves the All-Cause Mortality and Re-Hospitalization Rates in Acute Myocardial Infarction with Chronic Kidney Disease Patients.

作者信息

Qu Xiang, Yao Hui, Chen Changxi, Kong Shuting, Sun Lingyue, Du Leilei, Liang Siqi, Gao Zhan, Zheng Gaoshu, Zheng Minghua, Zhao Chuhuan, Feng Xiafei, Wu Gaojun, Zhou Hao

机构信息

Cardiovascular Medicine, First Affiliated Hospital of Wenzhou Medical University, The Key Lab of Cardiovascular Disease of Wenzhou, Wenzhou, China.

Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Front Pharmacol. 2021 May 31;12:632978. doi: 10.3389/fphar.2021.632978. eCollection 2021.

Abstract

Mineralocorticoid receptor antagonists (MRA) improve outcomes in chronic kidney disease (CKD) and acute myocardial infarction (AMI) patients. However, the lack of evidence regarding long-term clinical outcomes in the use of MRA, including spironolactone, in patients with AMI combined with CKD. This study aimed to investigate whether spironolactone could significantly reduce the risk of all-cause mortality and re-admission in patients with AMI and CKD. In this single center, observational, retrospective, registry based clinical study, a total of 2,465 AMI patients were initially screened; after excluding patients with estimated glomerular filtration rate more than 60 ml/min/1.73 m, 360 patients in the standard treatment group and 200 patients in the spironolactone group met the criteria. All enrolled patients follow-up for 30 months. The primary outcomes were all-cause mortality and re-admission. The key safety outcome was hyperkalemia rates during the 30 months follow-up period. 160 (44.4%) and 41 (20.5%) patients in the standard treatment and spironolactone groups died, respectively [hazard ratio (HR): 0.389; 95% confidence interval (CI): 0.276-0.548; < 0.001]. Re-admission occurred in 217 (60.3%) and 95 (47.5%) patients in the standard treatment and spironolactone groups, respectively (HR: 0.664; 95% CI: 0.522-0.846; = 0.004). The spironolactone group was divided into two based on the daily dose, low dose group (no more than 40 mg) and high dose group (more than 40 mg); the differences in the mortality rate between low dose group (16.7%) and the standard treatment group (44.4%) (HR: 0.309; 95% CI: 0.228-0.418; < 0.001) and high dose group (34.1%) (HR: 0.429; 95% CI: 0.199-0.925; = 0.007) were significant. The differences in re-hospitalization rate between low dose group (43.6%) and the standard treatment group (60.3%) (HR: 0.583; 95% CI: 0.457-0.744; < 0.001) and high dose group (61.4%) (HR: 0.551; 95% CI: 0.326-0.930; = 0.007) was significant. Hyperkalemia occurred in 18 (9.0%) and 18 (5.0%) patients in the spironolactone group and standard treatment group, respectively (HR: 1.879; 95% CI: 0.954-3.700; = 0.068). Whereas, Hyperkalemia occurred in high dose group (20.5%) significantly more often than in the standard treatment group ( < 0.001) and low dose group (5.8%) ( = 0.003). Using MRA, such as spironolactone, may substantially reduce the risk of both all-cause mortality and re-admission in patients with AMI and CKD; the use of low-dose spironolactone has the best efficacy and safety. However, this was a relatively small sample size, single center, observational, retrospective, registry based clinical study and further prospective evaluation in adequately powered randomized trials were needed before further use of spironolactone in AMI with CKD population.

摘要

盐皮质激素受体拮抗剂(MRA)可改善慢性肾脏病(CKD)和急性心肌梗死(AMI)患者的预后。然而,关于包括螺内酯在内的MRA用于AMI合并CKD患者的长期临床结局,目前仍缺乏证据。本研究旨在调查螺内酯是否能显著降低AMI合并CKD患者的全因死亡率和再次入院风险。在这项单中心、观察性、回顾性、基于登记处的临床研究中,最初筛查了2465例AMI患者;排除估算肾小球滤过率超过60 ml/min/1.73 m²的患者后,标准治疗组有360例患者,螺内酯组有200例患者符合标准。所有纳入患者随访30个月。主要结局为全因死亡率和再次入院。关键安全结局为随访30个月期间的高钾血症发生率。标准治疗组和螺内酯组分别有160例(44.4%)和41例(20.5%)患者死亡[风险比(HR):0.389;95%置信区间(CI):0.276 - 0.548;P < 0.001]。标准治疗组和螺内酯组分别有217例(60.3%)和95例(47.5%)患者再次入院(HR:0.664;95%CI:0.522 - 0.846;P = 0.004)。螺内酯组根据每日剂量分为两组,低剂量组(不超过40 mg)和高剂量组(超过40 mg);低剂量组(16.7%)与标准治疗组(44.4%)之间的死亡率差异(HR:0.309;95%CI:0.228 - 0.418;P < 0.001)以及与高剂量组(34.1%)之间的死亡率差异(HR:0.429;95%CI:0.199 - 0.925;P = 0.007)均具有显著性。低剂量组(43.6%)与标准治疗组(60.3%)之间的再住院率差异(HR:0.583;95%CI:0.45� - 0.744;P < 0.001)以及与高剂量组(61.4%)之间的再住院率差异(HR:0.551;95%CI:0.326 - 0.930;P = 0.007)具有显著性。螺内酯组和标准治疗组分别有18例(9.0%)和18例(5.0%)患者发生高钾血症(HR:1.879;95%CI:0.954 - 3.700;P = 0.068)。然而,高剂量组(20.5%)发生高钾血症的频率显著高于标准治疗组(P < 0.001)和低剂量组(5.8%)(P = 0.003)。使用MRA,如螺内酯,可能会大幅降低AMI合并CKD患者的全因死亡率和再次入院风险;使用低剂量螺内酯具有最佳的疗效和安全性。然而,这是一项样本量相对较小的单中心、观察性、回顾性、基于登记处的临床研究,在将螺内酯进一步用于AMI合并CKD人群之前,需要在足够样本量的前瞻性随机试验中进行进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efb0/8201517/2096852974b4/fphar-12-632978-g002.jpg

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