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Patiromer有助慢性肾病患者持久服用螺内酯
作者:小柯机器人 发布时间:2019/9/18 14:39:25

美国印第安纳大学Rajiv Agarwal小组取得一项新突破。他们发现钾结合剂Patiromer可使慢性肾病和难治性高血压患者更持久地服用螺内酯。2019年9月15日,相关论文在线发表在《柳叶刀》上。

2017年2月13日至2018年8月20日,这项多中心、临床2期、随机、双盲、安慰剂对照试验在十个国家(保加利亚、克罗地亚、格鲁吉亚、匈牙利、乌克兰、法国、德国、南非、英国、和美国)的62个门诊中心招募了574名患者。这些患者年龄均为18岁及以上,患有慢性肾病和难治性高血压,按照血清钾浓度和糖尿病病史进行分层,并按1:1随机分配接受安慰剂治疗或patiromer(每日8.4 g),两组患者均同时服用螺内酯和基础降压药。

共有295例(51%)患者符合所有标准,其中安慰剂组148例,patiromer组147例。在第12周,安慰剂组中有98例(66%)患者仍服用螺内酯,patiromer组有126例(86%),差异显著。安慰剂组中有79例(53%)患者发生不良反应,patiromer组有82例(56%),但均为轻度或中度。

Patiromer使得难治性高血压和慢性肾病的患者能够继续服用螺内酯,且很少发生高钾血症。

据悉,螺内酯可有效降低难治性高血压患者的血压。然而,其在慢性肾病患者中的使用可能受到高钾血症的限制。

附:英文原文

Title: Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial

Author: Rajiv Agarwal, Patrick Rossignol, Alain Romero, Dahlia Garza, Martha R Mayo, Suzette Warren, Jia Ma, William B White, Bryan Williams

Issue&Volume: 15 September 2019

Summary:

Background

Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension.

Methods

In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m 2) and uncontrolled resistant hypertension from 62 outpatient centres in ten countries (Bulgaria, Croatia, Georgia, Hungary, Ukraine, France, Germany, South Africa, the UK, and the USA). Patients meeting all eligibility criteria at the final screening visit were stratified by local serum potassium measurement (4·3 to <4·7 mmol/L vs 4·7 to 5·1 mmol/L) and history of diabetes. Participants were randomly assigned (1:1) with an interactive web response system to receive either placebo or patiromer (8·4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Participants, the study team that administered treatments and measured blood pressure, and the investigators were masked to assigned treatment groups. Dose titrations were permitted after 1 week (patiromer) and 3 weeks (spironolactone). The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomised patients (intention to treat). The study was registered with Clinicaltrials.gov, NCT03071263.

Findings

Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0–29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group.

Interpretation

In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension.

DOI: 10.1016/S0140-6736(19)32135-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32135-X/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet