Efficacy and safety of benazepril for advanced chronic renal insufficiency.
BACKGROUND
Angiotensin-converting-enzyme inhibitors provide renal protection in patients with mild-to-moderate renal insufficiency (serum creatinine level, 3.0 mg per deciliter or less). We assessed the efficacy and safety of benazepril in patients without diabetes who had advanced renal insufficiency.


METHODS
We enrolled 422 patients in a randomized, double-blind study. After an eight-week run-in period, 104 patients with serum creatinine levels of 1.5 to 3.0 mg per deciliter (group 1) received 20 mg of benazepril per day, whereas 224 patients with serum creatinine levels of 3.1 to 5.0 mg per deciliter (group 2) were randomly assigned to receive 20 mg of benazepril per day (112 patients) or placebo (112 patients) and then followed for a mean of 3.4 years. All patients received conventional antihypertensive therapy. The primary outcome was the composite of a doubling of the serum creatinine level, end-stage renal disease, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease.


RESULTS
Of 102 patients in group 1, 22 (22 percent) reached the primary end point, as compared with 44 of 108 patients given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in group 2 (60 percent). As compared with placebo, benazepril was associated with a 43 percent reduction in the risk of the primary end point in group 2 (P=0.005). This benefit did not appear to be attributable to blood-pressure control. Benazepril therapy was associated with a 52 percent reduction in the level of proteinuria and a reduction of 23 percent in the rate of decline in renal function. The overall incidence of major adverse events in the benazepril and placebo subgroups of group 2 was similar.


CONCLUSIONS
Benazepril conferred substantial renal benefits in patients without diabetes who had advanced renal insufficiency. (ClinicalTrials.gov number, NCT00270426.)
Hou
Fan Fan
FF
Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China. ffhou@public.guangzhou.gd.cn
Zhang
Xun
X
Zhang
Guo Hua
GH
Xie
Di
D
Chen
Ping Yan
PY
Zhang
Wei Ru
WR
Jiang
Jian Ping
JP
Liang
Min
M
Wang
Guo Bao
GB
Liu
Zheng Rong
ZR
Geng
Ren Wen
RW
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002681:China; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000401:mortality
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D003404:Creatinine; C044946:benazepril