Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.
Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.
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DOI：
10.1016/s1062-1458(03)00161-2
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发表时间：
2003-05
期刊：
影响因子：
168.9
通讯作者：
Naoyuki Nakao;A. Yoshimura;H. Morita;M. Takada;Tsuguo Kayano;T. Ideura
中科院分区：
文献类型：
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作者：
Naoyuki Nakao;A. Yoshimura;H. Morita;M. Takada;Tsuguo Kayano;T. Ideura
背景目前血管紧张素转换酶抑制剂治疗不能阻止非糖尿病肾病的进展。我们的目的是评估血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂联合治疗以及每种药物最大剂量单药治疗非糖尿病肾病患者的疗效和安全性。经过筛选和18周的导入期后，263例患者被随机分配接受血管紧张素II受体阻滞剂（氯沙坦，每日100 mg）、血管紧张素转换酶抑制剂（群多普利，每日3 mg）或等效剂量的两种药物联合治疗。进行生存分析，比较每种方案对血清肌酐浓度加倍或终末期肾病时间的联合主要终点的影响。分析是由意向treat.FindingsSeven患者停止或以其他方式失去了后续行动。85例接受联合治疗的患者中有10例（11%）达到了联合主要终点，相比之下，85例接受群多普利单药治疗的患者中有20例（23%）达到了联合主要终点（风险比0.38，95%CI 0.18 - 0.63，p= 0.018），86例接受氯沙坦单药治疗的患者中有20例（23%）达到了联合主要终点（0.40，0.17 - 0.69，p= 0.016）。影响肾存活率的协变量为联合治疗（风险比0.38，95% CI 0.18 - 0.63，p= 0.011），年龄（1·30，1·03-2·29，p=0·009），基线肾功能（1·80，1·02-2·99，p=0·021），每日尿蛋白排泄率的变化（0.58，0.24 - 0.88，p= 0.022），使用利尿剂（0.80，0.30 - 0.94，p= 0.043），群多普利抗蛋白尿反应（0.81，0.21 - 0.91，p= 0.039）。与单药治疗相比，联合治疗的副作用频率与群多普利单独治疗相同。然而，由于一些患者在联合治疗中达到了联合主要终点，因此需要研究进一步的策略来完全管理进行性非糖尿病肾病。
BackgroundPresent angiotensin-converting-enzyme inhibitor treatment fails to prevent progression of non-diabetic renal disease. We aimed to assess the efficacy and safety of combined treatment of angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker, and monotherapy of each drug at its maximumdose, in patients with non-diabetic renal disease.Methods336 patients with non-diabetic renal disease were enrolled from one renal outpatient department in Japan. After screening and an 18-week run-in period, 263 patients were randomly assigned angiotensin-II receptor blocker (losartan, 100 mg daily), angiotensin-converting-enzyme inhibitor (trandolapril, 3 mg daily), or a combination of both drugs at equivalent doses. Survival analysis was done to compare the effects of each regimen on the combined primary endpoint of time to doubling of serum creatinine concentration or end-stage renal disease. Analysis was by intention to treat.FindingsSeven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients on combination treatment reached the combined primary endpoint compared with 20 (23%) of 85 on trandolapril alone (hazard ratio 0·38, 95% CI 0·18–0·63, p=0·018) and 20 (23%) of 86 on losartan alone (0·40, 0·17–0·69, p=0·016). Covariates affecting renal survival were combination treatment (hazard ratio 0·38, 95% CI 0·18–0·63, p=0·011), age (1·30, 1·03–2·29, p=0·009), baseline renal function (1·80, 1·02–2·99, p=0·021), change in daily urinary protein excretion rate (0·58, 0·24–0·88, p=0·022), use of diuretics (0·80, 0·30–0·94, p=0·043), and antiproteinuric response to trandolapril (0·81, 0·21–0·91, p=0·039). Frequency of side-effects with combination treatment was the same as with trandolapril alone.InterpretationCombination treatment safely retards progression of non-diabetic renal disease compared with monotherapy. However, since some patients reached the combined primary endpoint on combined treatment, further strategies for complete management of progressive nondiabetic renal disease need to be researched.