沙库巴曲缬沙坦与厄贝沙坦对慢性肾脏病患者的影响。
Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease.
机构信息
Medical Research Council Population Health Research Unit (R.H., P.K.J., W.G.H., B.C.S., M.H., M.J.L., C.B.), University of Oxford, UK.
Clinical Trial Service Unit (R.H., P.K.J., N.S., W.G.H., B.C.S., L.B., M.H., M.J.L., C.B.), University of Oxford, UK.
出版信息
Circulation. 2018 Oct 9;138(15):1505-1514. doi: 10.1161/CIRCULATIONAHA.118.034818.
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 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, 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 among those assigned irbesartan; difference, -0.1 (0.7) mL/min/1.73 m. 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) mm Hg 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.
背景
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率，但在中重度慢性肾脏病患者中，其对肾功能和心脏生物标志物的影响尚不清楚。
方法
英国 HARP-III 试验（英国心脏和肾脏保护-III）是一项随机、双盲试验，纳入了估计肾小球滤过率（GFR）为 20 至 60 ml/min/1.73 m²的 414 名参与者，随机分为沙库巴曲缬沙坦 97/103 mg 每日 2 次组与厄贝沙坦 300 mg 每日 1 次组。主要结局是采用 ANCOVA 测定 12 个月时的肾小球滤过率，调整了每个个体的基线测量肾小球滤过率。所有分析均按意向治疗进行。
结果
共有 207 名参与者被分配至沙库巴曲缬沙坦组，207 名参与者被分配至厄贝沙坦组。基线测量的肾小球滤过率分别为 34.0（SE，0.8）和 34.7（SE，0.8）ml/min/1.73 m²。12 个月时，肾小球滤过率无差异：沙库巴曲缬沙坦组为 29.8（SE 0.5）ml/min/1.73 m²，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。在所有预先指定的亚组中，结果均相似。在 3、6、9 和 12 个月时，估计肾小球滤过率也无显著差异，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，沙库巴曲缬沙坦组的收缩压和舒张压分别降低了 5.4（95%CI，3.4-7.4）和 2.1（95%CI，1.0-3.3）mmHg，心肌肌钙蛋白 I 和脑钠肽前体 N 末端（次要终点）水平分别降低了 16%（95%CI，8-23）和 18%（95%CI，11-25）。严重不良事件（29.5%比 28.5%；发生率比，1.07；95%CI，0.75-1.53）、非严重不良反应（36.7%比 28.0%；发生率比，1.35；95%CI，0.96-1.90）和血钾≥5.5 mmol/L（32%比 24%，P=0.10）在随机分组之间无显著差异。
结论
在 12 个月时，沙库巴曲缬沙坦对肾功能和白蛋白尿的作用与厄贝沙坦相似，但对慢性肾脏病患者的血压和心脏生物标志物有额外的降低作用。
临床试验注册
网址：http://www.isrctn.com 。独特标识符：ISRCTN11958993。
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