Ruilope L M, Aldigier J C, Ponticelli C, Oddou-Stock P, Botteri F, Mann J F
Hospital 12 de Octubre, Servicio de Nefrologia, Madrid, Spain.
J Hypertens. 2000 Jan;18(1):89-95.
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.
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.
Serum creatinine increased in all three groups (mean change within a group: 11 micromol/l in group 1, P= 0.045; 9 micromol/l in group 2, P= 0.030; 15 micromol/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.
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.
多项实验和临床研究表明，肾素系统可能在肾脏疾病进展中起关键作用。与单独使用任一药物相比，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可对肾素 - 血管紧张素系统产生更高程度的阻断作用。这种增强的抑制作用可能对因慢性肾病导致肾功能进行性下降的患者有益。
在一组患有进行性慢性肾衰竭（肌酐清除率20 - 45 ml/分钟）、伴有或不伴有蛋白尿和高血压的患者中开展了一项初步的跨国、多中心、随机、活性对照、平行组开放标签研究。该研究的主要目的是调查缬沙坦和贝那普利联合使用的安全性和耐受性。患者被随机分配到三组中的一组：第1组每天服用一次缬沙坦160 mg（n = 22）；第2组每天服用一次缬沙坦80 mg加每天服用一次贝那普利5或10 mg（n = 42）；第3组每天服用一次缬沙坦160 mg加每天服用一次贝那普利5或10 mg（n = 44）。研究持续5周，在第2组和第3组中，在使用血管紧张素受体阻滞剂治疗第一周后，在缬沙坦基础上加用贝那普利。
三组患者的血清肌酐均升高（组内平均变化：第1组为11 μmol/l，P = 0.045；第2组为9 μmol/l，P = 0.030；第3组为15 μmol/l，P = 0.0006）。三组患者的血清钾也均升高（组内平均变化：第1组为0.28 mmol/l，P = 0.28；第2组为0.48 mmol/l，P = 0.0008；第3组为0.36 mmol/l，P = 0.02）。治疗5周后，第3组观察到最大的血压下降（坐位舒张压（SDBP）和坐位收缩压（SSBP）相对于基线的平均变化分别为：第1组为 - 2.0和 - 11.5 mmHg；第2组为 - 7.6和 - 15.4 mmHg；第3组为 - 12.6和 - 21.6 mmHg）。此外，两种联合治疗均导致蛋白尿减少。第1、2和3组发生不良事件的患者总数分别为10例（45.5%）、14例（33.3%）和11例（25%）。6例患者（5.6%）因不良事件而停药。联合治疗组中各有1例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。
这些结果表明，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使用对中度慢性肾衰竭患者是安全且耐受性良好的。
