Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
JAMA Intern Med. 2020 May 1;180(5):718-726. doi: 10.1001/jamainternmed.2020.0193.
It is uncertain whether and when angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) treatment should be discontinued in individuals with low estimated glomerular filtration rate (eGFR).
To investigate the association of ACE-I or ARB therapy discontinuation after eGFR decreases to below 30 mL/min/1.73 m2 with the risk of mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD).
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, propensity score-matched cohort study included 3909 patients from an integrated health care system that served rural areas of central and northeastern Pennsylvania. Patients who initiated ACE-I or ARB therapy from January 1, 2004, to December 31, 2018, and had an eGFR decrease to below 30 mL/min/1.73 m2 during therapy were enrolled, with follow-up until January 25, 2019.
Individuals were classified based on whether they discontinued ACE-I or ARB therapy within 6 months after an eGFR decrease to below 30 mL/min/1.73 m2.
The association between ACE-I or ARB therapy discontinuation and mortality during the subsequent 5 years was assessed using multivariable Cox proportional hazards regression models, adjusting for patient characteristics at the time of the eGFR decrease in a propensity score-matched sample. Secondary outcomes included MACE and ESKD.
Of the 3909 individuals receiving ACE-I or ARB treatment who experienced an eGFR decrease to below 30 mL/min/1.73 m2 (2406 [61.6%] female; mean [SD] age, 73.7 [12.6] years), 1235 discontinued ACE-I or ARB therapy within 6 months after the eGFR decrease and 2674 did not discontinue therapy. A total of 434 patients (35.1%) who discontinued ACE-I or ARB therapy and 786 (29.4%) who did not discontinue therapy died during a median follow-up of 2.9 years (interquartile range, 1.3-5.0 years). In the propensity score-matched sample of 2410 individuals, ACE-I or ARB therapy discontinuation was associated with a higher risk of mortality (hazard ratio [HR], 1.39; 95% CI, 1.20-1.60]) and MACE (HR, 1.37; 95% CI, 1.20-1.56), but no statistically significant difference in the risk of ESKD was found (HR, 1.19; 95% CI, 0.86-1.65).
The findings suggest that continuing ACE-I or ARB therapy in patients with declining kidney function may be associated with cardiovascular benefit without excessive harm of ESKD.
目前尚不确定在肾小球滤过率（eGFR）降低至 30ml/min/1.73m2 以下的个体中，是否以及何时应停止使用血管紧张素转换酶抑制剂（ACE-I）和血管紧张素 II 受体阻滞剂（ARB）治疗。
研究在 eGFR 下降至 30ml/min/1.73m2 以下后，停止 ACE-I 或 ARB 治疗与死亡率、主要不良心血管事件（MACE）和终末期肾病（ESKD）风险之间的关系。
设计、设置和参与者：这是一项回顾性、倾向评分匹配队列研究，纳入了来自宾夕法尼亚州中北部农村地区的一个综合医疗保健系统的 3909 名患者。研究纳入了从 2004 年 1 月 1 日至 2018 年 12 月 31 日开始接受 ACE-I 或 ARB 治疗且治疗期间 eGFR 下降至 30ml/min/1.73m2 以下的患者，随访至 2019 年 1 月 25 日。
根据患者在 eGFR 下降至 30ml/min/1.73m2 以下后 6 个月内是否停止 ACE-I 或 ARB 治疗，对患者进行分类。
使用多变量 Cox 比例风险回归模型评估 ACE-I 或 ARB 治疗停止与随后 5 年内死亡率之间的关系，在倾向评分匹配样本中，根据 eGFR 下降时的患者特征进行调整。次要结局包括 MACE 和 ESKD。
在接受 ACE-I 或 ARB 治疗且 eGFR 下降至 30ml/min/1.73m2 以下的 3909 名患者中（2406 [61.6%] 为女性；平均[SD]年龄为 73.7[12.6]岁），有 1235 名患者在 eGFR 下降后 6 个月内停止 ACE-I 或 ARB 治疗，2674 名患者未停止治疗。共有 434 名（35.1%）停止 ACE-I 或 ARB 治疗的患者和 786 名（29.4%）未停止治疗的患者在中位随访 2.9 年（四分位距，1.3-5.0 年）期间死亡。在 2410 名倾向评分匹配患者的样本中，ACE-I 或 ARB 治疗停止与死亡率（风险比[HR]，1.39；95%CI，1.20-1.60）和 MACE（HR，1.37；95%CI，1.20-1.56）的风险增加相关，但与 ESKD 风险无统计学显著差异（HR，1.19；95%CI，0.86-1.65）。
研究结果表明，在肾功能下降的患者中继续使用 ACE-I 或 ARB 治疗可能与心血管获益相关，而不会对 ESKD 造成过度危害。
