University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill, NC; Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC.
Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC.
Am J Kidney Dis. 2018 Sep;72(3):337-348. doi: 10.1053/j.ajkd.2018.02.350. Epub 2018 Apr 10.
Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population.
A retrospective cohort study using a new-user design.
SETTING & PARTICIPANTS: Medicare-enrolled hemodialysis patients treated at a large US dialysis organization who initiated carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012.
Carvedilol versus metoprolol initiation.
All-cause mortality, cardiovascular mortality, and intradialytic hypotension (systolic blood pressure decrease ≥ 20mmHg during hemodialysis plus intradialytic saline solution administration) during a 1-year follow-up period.
Survival models were used to estimate HRs and 95% CIs in mortality analyses. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in intradialytic hypotension analyses. Inverse probability of treatment weighting was used to adjust for several demographic, clinical, laboratory, and dialysis treatment covariates in all analyses.
27,064 individuals receiving maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and 17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup analyses, similar associations were observed among patients with hypertension, atrial fibrillation, heart failure, and a recent myocardial infarction, the main cardiovascular indications for β-blocker therapy. During follow-up, carvedilol (vs metoprolol) initiators had a higher rate of intradialytic hypotension (adjusted IRR, 1.10; 95% CI, 1.09-1.11).
Residual confounding may exist.
Relative to metoprolol initiation, carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality. One potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.
卡维地洛和美托洛尔是美国血液透析患者最常开的β受体阻滞剂，占β受体阻滞剂处方的 80%左右。尽管这两种药物在药理学和药代动力学方面有明显的差异，但在血液透析人群中，它们的相对安全性和疗效知之甚少。
这是一项回顾性队列研究，采用新用户设计。
医疗保险覆盖的血液透析患者，在一家大型美国透析机构接受治疗，他们在 2007 年 1 月 1 日至 2012 年 12 月 30 日期间开始使用卡维地洛或美托洛尔治疗。
卡维地洛与美托洛尔的起始使用。
在 1 年的随访期间，全因死亡率、心血管死亡率和透析期间低血压（透析期间血液透析加透析液中生理盐水给药时收缩压下降≥20mmHg）。
生存模型用于估计死亡率分析中的 HR 和 95%置信区间。泊松回归用于估计透析期间低血压分析中的发病率比（IRR）和 95%置信区间。在所有分析中，逆概率治疗权重用于调整几个人口统计学、临床、实验室和透析治疗协变量。
纳入 27064 名接受维持性血液透析的患者：卡维地洛起始组 9558 例（35.3%），美托洛尔起始组 17506 例（64.7%）。与美托洛尔相比，卡维地洛起始治疗与全因死亡率（调整 HR，1.08；95%CI，1.02-1.16）和心血管死亡率（调整 HR，1.18；95%CI，1.08-1.29）增加相关。在亚组分析中，在高血压、心房颤动、心力衰竭和近期心肌梗死的患者中也观察到类似的相关性，β受体阻滞剂治疗的主要心血管适应证。在随访期间，与美托洛尔相比，卡维地洛起始治疗组透析期间低血压的发生率更高（调整 IRR，1.10；95%CI，1.09-1.11）。
可能存在残余混杂。
与美托洛尔相比，卡维地洛起始治疗与 1 年全因和心血管死亡率增加相关。这些发现的一个潜在机制可能是卡维地洛（与美托洛尔相比）起始治疗后透析期间低血压的发生率增加。
