Safety of the combination of valsartan and benazepril in patients with chronic renal disease

Objective Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combinati on of an angiotensin-converting enzyme inhibitor and an angiotensin recepto r blocker could provide a higher degree of blockade of the renin-angiotensi n system than either agent alone. Such enhanced suppression might be of ben efit for patients exhibiting a progressive decline in renal function becaus e 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 w ith progressive chronic renal failure (creatinine clearance 20-45 ml/min) e ither 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 g roups: group 1 received valsartan 160 mg once daily (n = 22); group 2 recei ved valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily (n = 4 2); 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 b enazepril was added on top of valsartan after the first week of therapy wit h 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 = 0.03 0; 15 mu mol/l in group 3, P = 0.0006). Serum potassium also increased in a ll three groups of patients (mean change within a group: 0.28 mmol/l in gro up 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 press ure was observed in group 3 (the mean change from baseline in seated diasto lic blood pressure (SDBP) and seated systolic blood pressure (SSBP), respec tively, 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 treatmen ts resulted in the reduction of proteinuria. The total number of patients w ith 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 a s a result of adverse experiences. Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no pat ients were forced to withdraw because of an increase in serum creatinine, a cute renal failure or hospitalization. Conclusions These results indicate that short-term combination of an angiot ensin-converting enzyme inhibitor and an angiotensin receptor blocker is sa fe and well tolerated in patients with moderate chronic renal failure. J Hy pertens 2000, 18:89-95 (C) Lippincott Williams & Wilkins.