Safety of the combination of valsartan and benazepril in patients with chronic renal disease
Safety of the combination of valsartan and benazepril in patients with chronic renal disease
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DOI：
10.1097/00004872-200018010-00013
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发表时间：
2000-01-01
影响因子：
4.9
通讯作者：
Mann, JF
中科院分区：
文献类型：
--
作者：
Ruilope, LM;Aldigier, JC;Mann, JF
目的多项实验和临床研究表明，肾素系统在肾脏疾病进展中可能起关键作用。血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂联合使用比单独使用任何一种药物都能提供更高程度的肾素-血管紧张素系统阻断。这种增强的抑制可能对慢性肾脏疾病导致肾功能进行性下降的患者有益。方法在一组伴有或不伴有蛋白尿和高血压的进行性慢性肾功能衰竭（肌酐清除率20-45 ml/min）患者中进行了一项多国、多中心、随机、主动对照、平行组开放标签研究。该研究的主要目的是调查缬沙坦和苯那普利联合使用的安全性和耐受性。患者被随机分为三组：第一组接受缬沙坦160 mg，每日一次（n = 22）；2组服用缬沙坦80 mg / d +贝那普利5或10 mg / d (n = 42)；3组患者给予缬沙坦160 mg / d +贝那普利5或10 mg / d (n = 44)，研究持续5周，2组和3组患者在血管紧张素受体阻滞剂治疗第1周后在缬沙坦基础上加用贝那普利。结果3组血清肌酐均升高（组内平均变化：1组11 mu mol/l， P = 0.045； 2组9 mu mol/l， P = 0.030； 3组15 mu mol/l， P = 0.0006）。三组患者血清钾均升高（组内平均变化：1组0.28 mmol/l, P = 0.28； 2组0.48 mmol/l, P = 0.0008； 3组0.36 mmol/l, P = 0.02）。治疗5周后，第3组血压下降幅度最大(与基线相比，第1组坐位舒张压（SDBP）和坐位收缩压（SSBP）的平均变化分别为-2.0和-11.5 mmHg；-7.6和-15.4 mmHg组2；-12.6和-21.6 mmHg)。此外，两种联合治疗均可减少蛋白尿。1、2、3组不良反应患者总数分别为10例（45.5%）、14例（33.3%）、11例（25%）。6例（5.6%）患者因不良反应而停止治疗。每个联合治疗组中只有一名患者因高钾血症退出研究，没有患者因血清肌酐升高、急性肾衰竭或住院而被迫退出研究。结论血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂短期联合治疗中度慢性肾功能衰竭是安全且耐受性良好的。[J]李志强，李志强。中国生物医学工程学报，2009,18(3):559 - 564。
Objective Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin system than either agent alone. Such enhanced suppression might be of benefit for patients exhibiting a progressive decline in renal function because of chronic renal disease.Methods A pilot multinational, multicentre, randomized, active-controlled, parallel group open-label study has been conducted in a group of patients with progressive chronic renal failure (creatinine clearance 20-45 ml/min) either with or without proteinuria and hypertension. The primary aim of the study was to investigate the safety and tolerability of the combination of valsartan and benazepril. Patients were randomly assigned to one of three groups: group 1 received valsartan 160 mg once daily (n = 22); group 2 received valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily (n = 42); group 3 received valsartan 160 mg once daily plus benazepril 5 or 10 mg once daily (n = 44), The study lasted for 5 weeks, and in groups 2 and 3 benazepril was added on top of valsartan after the first week of therapy with the angiotensin receptor blocker.Results Serum creatinine increased in all three groups (mean change within a group: 11 mu mol/l in group 1, P = 0.045; 9 mu mol/l in group 2, P = 0.030; 15 mu mol/l in group 3, P = 0.0006). Serum potassium also increased in all three groups of patients (mean change within a group: 0.28 mmol/l in group 1, P = 0.28; 0.48 mmol/l in group 2, P = 0.0008; 0.36 mmol/l in group 3, P = 0.02). After 5 weeks of treatment, the largest decrease in blood pressure was observed in group 3 (the mean change from baseline in seated diastolic blood pressure (SDBP) and seated systolic blood pressure (SSBP), respectively, were: -2.0 and -11.5 mmHg in group 1; -7.6 and -15.4 mmHg in group 2; -12.6 and -21.6 mmHg in group 3). In addition, both combination treatments resulted in the reduction of proteinuria. The total number of patients with adverse experiences were 10 (45.5%), 14 (33.3%) and 11 (25%) in groups 1, 2 and 3, respectively. In six patients (5.6%) therapy was discontinued as a result of adverse experiences. Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no patients were forced to withdraw because of an increase in serum creatinine, acute renal failure or hospitalization.Conclusions These results indicate that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure. J Hypertens 2000, 18:89-95 (C) Lippincott Williams & Wilkins.