University of Maryland School of Medicine, Baltimore, MD, USA.
Circ Heart Fail. 2011 Jan;4(1):18-26. doi: 10.1161/CIRCHEARTFAILURE.109.932558. Epub 2010 Oct 29.
The safety and efficacy of different types of β-blocker therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and systolic heart failure (HF) are not well described. We assessed whether treatment of systolic HF with carvedilol is efficacious and safe in adults with CKD.
We performed a post hoc analysis of pooled individual patient data (n=4217) from 2 multinational, double-blinded, placebo-controlled, randomized trials, CAPRICORN (Carvedilol Postinfarct Survival Control in Left Ventricular Dysfunction Study) and COPERNICUS (Carvedilol Prospective Randomized, Cumulative Survival study). Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, HF mortality, first HF hospitalization, the composite of cardiovascular mortality or first HF hospitalization, and sudden cardiac death. Non-dialysis-dependent CKD was defined by estimated glomerular filtration rate ≤60 mL/min/1.73 m(2), using the abbreviated Modification of Diet in Renal Disease equation. CKD was present in 2566 of 4217 (60.8%) of the cohort, 50.4% of whom were randomly assigned to carvedilol therapy. Within the CKD group, treatment with carvedilol decreased the risks of all-cause mortality (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63 to 0.93; P=0.007), cardiovascular mortality (HR, 0.76; 95% CI, 0.62 to 0.94; P=0.011), HF mortality (HR, 0.68; 95% CI, 0.52 to 0.88; P=0.003), first hospitalization for HF (HR, 0.74; 95% CI, 0.61 to 0.88; P=0.0009), and the composite of cardiovascular mortality or HF hospitalization (HR, 0.75; 95% CI, 0.65 to 0.87; P<0.001) but was without significant effect on sudden cardiac death (HR, 0.76; 95% CI, 0.56 to 1.05; P=0.098). There was no significant interaction between treatment arm and study type. Carvedilol was generally well tolerated by both groups of patients, with an increased relative incidence in transient increase in serum creatinine without need for dialysis and other electrolyte changes in the CKD patients. However, in a sensitivity analysis among HF subjects with estimated glomerular filtration rate <45 mL/min/1.73 m(2) (CKD stage 3b), the efficacy of carvedilol was not significantly different from placebo.
This analysis suggests that the benefits of carvedilol therapy in patients with systolic left ventricular dysfunction with or without symptoms of HF are consistent even in the presence of mild to moderate CKD. Whether carvedilol therapy is similarly efficacious in HF patients with more advanced kidney disease requires further study.
不同类型β受体阻滞剂在非透析依赖型慢性肾脏病（CKD）和收缩性心力衰竭（HF）患者中的安全性和疗效尚未得到充分描述。我们评估了卡维地洛治疗收缩性 HF 在 CKD 成人中的疗效和安全性。
我们对来自 2 项多中心、双盲、安慰剂对照、随机临床试验（CAPRICORN[卡维地洛心梗后存活控制左心室功能障碍研究]和 COPERNICUS[卡维地洛前瞻性随机累积存活研究]）的合并患者个体数据（n=4217）进行了事后分析。主要结局是全因死亡率。次要结局包括心血管死亡率、HF 死亡率、首次 HF 住院、心血管死亡率或首次 HF 住院的复合终点以及心源性猝死。通过简化肾脏病饮食改良公式估计肾小球滤过率（eGFR）≤60 mL/min/1.73 m2 定义非透析依赖型 CKD。4217 例患者中有 2566 例（60.8%）存在 CKD，其中 50.4%被随机分配至卡维地洛治疗组。在 CKD 组中，卡维地洛治疗降低了全因死亡率（风险比[HR]，0.76；95%置信区间[CI]，0.63 至 0.93；P=0.007）、心血管死亡率（HR，0.76；95%CI，0.62 至 0.94；P=0.011）、HF 死亡率（HR，0.68；95%CI，0.52 至 0.88；P=0.003）、HF 首次住院率（HR，0.74；95%CI，0.61 至 0.88；P=0.0009）以及心血管死亡率或 HF 住院的复合终点（HR，0.75；95%CI，0.65 至 0.87；P<0.001），但对心源性猝死无显著影响（HR，0.76；95%CI，0.56 至 1.05；P=0.098）。治疗组与研究类型之间无显著交互作用。两组患者均能较好耐受卡维地洛治疗，在 CKD 患者中出现一过性血清肌酐升高且无需透析以及其他电解质变化的相对发生率增加。然而，在肾小球滤过率估计值<45 mL/min/1.73 m2（CKD 3b 期）的 HF 患者中进行的敏感性分析中，卡维地洛的疗效与安慰剂无显著差异。
本分析表明，卡维地洛治疗左心室收缩功能障碍伴或不伴 HF 症状患者的疗效在存在轻度至中度 CKD 时是一致的。卡维地洛治疗在更严重的肾脏病 HF 患者中是否同样有效，尚需进一步研究。
