Yang Aimin, Shi Mai, Lau Eric S H, Wu Hongjiang, Zhang Xinge, Fan Baoqi, Kong Alice P S, Luk Andrea O Y, Ma Ronald C W, Chan Juliana C N, Chow Elaine
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
EClinicalMedicine. 2022 Nov 24;55:101751. doi: 10.1016/j.eclinm.2022.101751. eCollection 2023 Jan.
Renin-angiotensin-system inhibitors (RASi), that include angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay chronic kidney disease (CKD) progression, protect against cardiovascular events and heart failure hospitalizations. We examined the associations of discontinuation of ACEi/ARBs with risk of clinical outcomes in Chinese patients with type 2 diabetes (T2D) and advanced-CKD (estimated-glomerular filtration rate [eGFR] <30 ml/min/1.73 m).
We conducted a prospective, population-based cohort study including 10,400 patients with T2D in Hong Kong stratified by continuation of ACEi/ARBs within 6 months after reaching eGFR <30 ml/min/1.73 m from January 01, 2002 to December 31, 2018 and observed until December 31, 2019. The primary outcomes were death, major-adverse cardiovascular events (MACE), heart failure, end-stage kidney disease (ESKD), and all-cause mortality. Cox-model with time-dependent exposure and covariates was used to estimate the hazard ratio (HR) of outcomes in a propensity-score overlap-weighted cohort. The risk of occurrence of hyperkalemia (plasma potassium >5.5 mmol/L) in discontinued-ACEi/ARBs versus continued-ACEi/ARBs users was assessed in a register-based cohort.
In the population-based cohort of 10,400 ACEi/ARBs users with new-onset eGFR<30 ml/min/1.73 m, 1766 (17.0%) discontinued ACEi/ARBs and 8634 (83.0%) persisted with treatment. During a median follow-up of 3.6 (interquartile range, IQR: 2.11-5.8) years (41,623 person-years), 13.5%, 12.9%, and 27.6% had incident MACE, heart failure and ESKD respectively, and 35.8% died. Discontinued-ACEi/ARBs use was associated with higher risk of MACE (HR = 1.27, 95% CI: 1.08-1.49), heart failure (HR = 1.85, 95% CI: 1.53-2.25) and ESKD (HR = 1.30, 95% CI: 1.17-1.43), and neutral risk of all-cause mortality (HR = 0.93, 95% CI: 0.86-1.01) compared to counterparts with continued use. In the register-based cohort (583 discontinued-ACEi/ARBs users and 3817 continued-ACEi/ARBs users), discontinued-ACEi/ARBs had neutral risk of hyperkalemia (HR = 0.95, 95% CI: 0.84-1.08).
Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events supporting their continued use in patients with T2D and advanced-CKD.
CUHK Impact Research Fellowship Scheme.
肾素-血管紧张素系统抑制剂（RASi），包括血管紧张素转换酶抑制剂（ACEi）和血管紧张素受体阻滞剂（ARB），可减少蛋白尿、延缓慢性肾脏病（CKD）进展、预防心血管事件和心力衰竭住院。我们研究了中国2型糖尿病（T2D）合并晚期CKD（估计肾小球滤过率[eGFR]<30 ml/min/1.73 m²）患者停用ACEi/ARB与临床结局风险之间的关联。
我们进行了一项基于人群的前瞻性队列研究，纳入了2002年1月1日至2018年12月31日期间香港10400例T2D患者，根据eGFR<30 ml/min/1.73 m²后6个月内ACEi/ARB的使用情况进行分层，并随访至2019年12月31日。主要结局为死亡、主要不良心血管事件（MACE）、心力衰竭、终末期肾病（ESKD）和全因死亡率。采用具有时间依赖性暴露和协变量的Cox模型，在倾向评分重叠加权队列中估计结局的风险比（HR）。在基于登记的队列中评估停用ACEi/ARB与继续使用ACEi/ARB的患者发生高钾血症（血钾>5.5 mmol/L）的风险。
在10400例新发生eGFR<30 ml/min/1.73 m²的ACEi/ARB使用者的人群队列中，1766例（17.0%）停用了ACEi/ARB，8634例（83.0%）继续治疗。在中位随访3.6（四分位间距，IQR：2.11-5.8）年（41623人年）期间，分别有13.5%、12.9%和27.6%的患者发生了MACE、心力衰竭和ESKD，35.8%的患者死亡。与继续使用的患者相比，停用ACEi/ARB与MACE（HR = 1.27，95%CI：1.08-1.49）、心力衰竭（HR = 1.85，95%CI：1.53-2.25）和ESKD（HR = 1.30，95%CI：1.17-1.43）的风险增加相关，而与全因死亡率的风险无差异（HR = 0.93，95%CI：0.86-1.01）。在基于登记的队列中（583例停用ACEi/ARB的患者和3817例继续使用ACEi/ARB的患者），停用ACEi/ARB发生高钾血症的风险无差异（HR = 0.95，95%CI：0.84-1.08）。
停用ACEi/ARB与心血管-肾脏事件风险增加相关，支持其在T2D合并晚期CKD患者中继续使用。
香港中文大学影响力研究奖学金计划。
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