2758
document
Safety of the combination of valsartan and benazepril in patients with chronic renal disease . European Group for the Investigation of Valsartan in Chronic Renal Disease . 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 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 . 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 .
2759
Intervention_Pharmacological
combination of valsartan
2760
Intervention_Pharmacological
benazepril
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Intervention_Pharmacological
Valsartan
2762
Intervention_Pharmacological
combination of valsartan
2763
Intervention_Pharmacological
benazepril
2764
Intervention_Pharmacological
valsartan 160 mg
2765
Intervention_Pharmacological
valsartan 80 mg once daily
2766
Intervention_Pharmacological
benazepril 5 or 10 mg once daily
2767
Intervention_Pharmacological
valsartan 160 mg
2768
Intervention_Pharmacological
benazepril 5 or 10 mg
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Outcome_Other
Safety
2770
Outcome_Other
safety and tolerability
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Outcome_Physical
Serum creatinine
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Outcome_Physical
Serum potassium
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Outcome_Physical
blood pressure
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Outcome_Physical
seated diastolic blood pressure ( SDBP )
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Outcome_Physical
seated systolic blood pressure ( SSBP )
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Outcome_Physical
proteinuria
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Outcome_Adverse-effects
adverse experiences
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Outcome_Physical
hyperkalaemia
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Outcome_Physical
serum creatinine
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Outcome_Physical
acute renal failure
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Outcome_Other
hospitalization
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Outcome_Other
safe
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Outcome_Other
well tolerated
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Participant_Condition
chronic renal disease
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Participant_Condition
progressive decline in renal function
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Participant_Condition
chronic renal disease
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Participant_Sample-size
22
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Participant_Sample-size
42
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Participant_Sample-size
44