Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease: A Randomized Double-Blind Trial
Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease: A Randomized Double-Blind Trial
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DOI：
10.1161/circulationaha.118.034818
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发表时间：
2018-10-09
期刊：
影响因子：
37.8
通讯作者：
Baigent, Colin
中科院分区：
文献类型：
--
作者：
Haynes, Richard;Judge, Parminder K.;Baigent, Colin
背景资料：沙库巴曲/缬沙坦可降低射血分数降低的心力衰竭患者的心血管死亡风险，但其对中重度慢性肾脏疾病患者的肾功能和心脏生物标志物的影响尚不清楚。英国HARP-III试验（英国心脏和肾脏保护-III），一项随机双盲试验，包括414名肾小球滤过率（GFR）估计值为20 - 60 mL/min/1.73 m2的受试者，他们被随机分配到沙库巴曲/缬沙坦97/103 mg，每日2次组和厄贝沙坦300 mg，每日1次组。主要结果是使用ANCOVA测量12个月时的GFR，并对每个人的基线测量GFR进行调整。所有的分析都是由意向treat.Results：总共，207名参与者被分配到沙库巴曲/缬沙坦和207厄贝沙坦。基线测量的GFR分别为34.0（SE，0.8）和34.7（SE，0.8）mL/min/1.73 m2。在12个月时，测得的GFR没有差异：沙库巴曲/缬沙坦组为29.8（SE 0.5），厄贝沙坦组为29.9（SE 0.5）mL/min/1.73 m2;差异为-0.1（0.7）mL/min/1.73 m2。在所有预先规定的亚组中，效应相似。第3、6、9或12个月时的GFR估计值也无显著差异，治疗组之间的尿白蛋白：肌酐比值也无明显差异（研究平均差异，-9%; 95% CI，-18至1）。然而，与厄贝沙坦相比，沙库比曲/缬沙坦组的研究平均收缩压和舒张压降低了5.4（95% CI，3.4-7.4）和2.1（95% CI，1.0-3.3）mmHg和激素原脑钠肽的肌钙蛋白I和N末端水平（三级终点）分别降低16%（95% CI，8-23）和18%（95% CI，11-25）。严重不良事件的发生率（29.5% vs 28.5%;率比，1.07; 95% CI，0.75-1.53），非严重不良反应（36.7% vs 28.0%;率比，1.35; 95% CI，0.96-1.90），钾5.5 mmol/L（32%对24%，P=0.10）在随机分组之间没有显著差异。在12个月内，沙库巴曲/缬沙坦对肾功能和蛋白尿的影响与厄贝沙坦相似，但它具有降低慢性肾病患者血压和心脏生物标志物的额外作用。临床试验注册：网址：http://www.isrctn.com。唯一标识符：ISRCTN 11958993。
Background: Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with moderate to severe chronic kidney disease are unknown.Methods: The UK HARP-III trial (United Kingdom Heart and Renal Protection-III), a randomized double-blind trial, included 414 participants with an estimated glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m(2) who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily. The primary outcome was measured GFR at 12 months using ANCOVA with adjustment for each individual's baseline measured GFR. All analyses were by intention to treat.Results: In total, 207 participants were assigned to sacubitril/valsartan and 207 to irbesartan. Baseline measured GFR was 34.0 (SE, 0.8) and 34.7 (SE, 0.8) mL/min/1.73 m(2), respectively. At 12 months, there was no difference in measured GFR: 29.8 (SE 0.5) among those assigned sacubitril/valsartan versus 29.9 (SE, 0.5) mL/min/1.73 m(2) among those assigned irbesartan; difference, -0.1 (0.7) mL/min/1.73 m(2). Effects were similar in all prespecified subgroups. There was also no significant difference in estimated GFR at 3, 6, 9, or 12 months and no clear difference in urinary albumin:creatinine ratio between treatment arms (study average difference, -9%; 95% CI, -18 to 1). However, compared with irbesartan, allocation to sacubitril/valsartan reduced study average systolic and diastolic blood pressure by 5.4 (95% CI, 3.4-7.4) and 2.1 (95% CI, 1.0-3.3) mmHg and levels of troponin I and N terminal of prohormone brain natriuretic peptide (tertiary end points) by 16% (95% CI, 8-23) and 18% (95% CI, 11-25), respectively. The incidence of serious adverse events (29.5% versus 28.5%; rate ratio, 1.07; 95% CI, 0.75-1.53), nonserious adverse reactions (36.7% versus 28.0%; rate ratio, 1.35; 95% CI, 0.96-1.90), and potassium 5.5 mmol/L (32% versus 24%, P=0.10) was not significantly different between randomized groups.Conclusions: Over 12 months, sacubitril/valsartan has similar effects on kidney function and albuminuria to irbesartan, but it has the additional effect of lowering blood pressure and cardiac biomarkers in people with chronic kidney disease.Clinical Trial Registration: URL: http://www.isrctn.com. Unique identifier: ISRCTN11958993.