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α 受体阻滞剂与 CKD 患者的肾脏、心脏和安全性结局:基于人群的队列研究。

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

机构信息

Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.

Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.

出版信息

Am J Kidney Dis. 2021 Feb;77(2):178-189.e1. doi: 10.1053/j.ajkd.2020.07.018. Epub 2020 Sep 11.

Abstract

RATIONALE & OBJECTIVES: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown.

STUDY DESIGN

Population-based retrospective cohort study.

SETTINGS & PARTICIPANTS: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB.

EXPOSURES

New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication.

OUTCOMES

30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality.

ANALYTICAL APPROACH

New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m) were explored.

RESULTS

Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m, respectively.

LIMITATIONS

Observational design, BP measurement data unavailable.

CONCLUSIONS

AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

摘要

背景与目的

α受体阻滞剂(ABs)常用于治疗伴有或不伴有慢性肾脏病(CKD)的耐药或难治性高血压患者。AB 类药物的使用与 CKD 患者的肾脏、心脏、死亡率和安全性相关结局之间的关系尚不清楚。

研究设计

基于人群的回顾性队列研究。

地点与参与者

2007 年至 2015 年期间,在安大略省(加拿大)居住的年龄在 66 岁及以上且没有 AB 类药物处方的高血压患者。

暴露因素

新使用 AB 类药物与新使用非 AB 类降压药物。

结局

估算肾小球滤过率(eGFR)下降 30%或以上;开始透析或肾脏移植(肾脏替代治疗);急性心肌梗死、冠状动脉血运重建、充血性心力衰竭或心房颤动的复合结局;安全性(低血压、晕厥、跌倒和骨折)事件;以及死亡率。

分析方法

使用高维倾向评分对 AB 类药物(多沙唑嗪、特拉唑嗪和哌唑嗪)的新使用者进行匹配,以匹配非 AB 类药物的新使用者。使用 Cox 比例风险和 Fine 和 Gray 模型来研究 AB 类药物使用与肾脏、心脏、死亡率和安全性结局之间的关联。探索了 eGFR 类别(≥90、60-89、30-59 和<30mL/min/1.73m)的交互作用。

结果

在 381120 名符合条件的个体中,有 16088 名患者被分配了 AB 类药物,并与非 AB 类药物使用者 1:1 匹配。AB 类药物的使用与 eGFR 下降 30%或以上的风险增加相关(HR,1.14;95%CI,1.08-1.21)和需要肾脏替代治疗的风险增加(HR,1.28;95%CI,1.13-1.44)。eGFR 水平没有改变这些关联,P 交互作用值分别为 0.3 和 0.3。相反,AB 类药物的使用与心脏事件的风险降低相关,这在 eGFR 类别中也是一致的(HR,0.92;95%CI,0.89-0.95;P 交互作用值为 0.1)。AB 类药物的使用还与较低的死亡率风险相关,但仅在 eGFR<60mL/min/1.73m 的患者中(P 交互作用值<0.001):HR 分别为 0.85(95%CI,0.78-0.93)和 0.71(95%CI,0.64-0.80)。

局限性

观察性设计,BP 测量数据不可用。

结论

与其他降压药物相比,CKD 患者使用 AB 类药物与肾脏疾病进展风险增加相关,但与心脏事件和死亡率风险降低相关。

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