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Abstract

To test the efficacy and tolerability of long-term administration of the angiotensin converting enzyme inhibitor, benazepril, in dogs with heart failure.

METHODS:

The study was a prospective, randomized, double-blind, placebo-controlled clinical trial involving 16 centers in France, Italy, Switzerland and UK. A total of 162 dogs with class II and III (ISACHC classification) heart failure caused by chronic valvular disease (CVD) or dilated cardiomyopathy (DCM) were enrolled. Benazepril (minimum dosage, 0.25 mg/kg) or placebo were administered orally once daily for up to 34 months, either alone or as add-on therapy to "standard therapy" i.e. diuretics and/or digoxin and/or anti-arrhythmic drugs.

RESULTS:

The mean survival time (to death or withdrawal from the study due to worsening of heart failure) was 2.7 times longer in the benazepril treated group (428 days) as compared with the placebo group (158 days). Differences reached statistical significance (p<0.05 Cox proportional hazards model, 44% reduction in risk). The survival rate after one year was 49% with benazepril and 20% with placebo. Benazepril produced a statistically significant (p<0.05) reduction (by 46%) in the risk of worsening of heart failure (to ISACHC class III) when therapy was initiated early (in ISACHC class II). In sub-group analyses, a statistically significant (p<0.05) benefit of benazepril was reached for both survival and worsening endpoints for dogs with CVD (n=125), but not for the small sample of dogs with DCM (37). Benazepril also improved the exercise tolerance and global clinical condition at day 28 (p<0.05). As compared to the placebo group, dogs treated with benazepril presented with the same frequency of undesirable clinical events and fewer biochemical disturbances (less frequent increases in plasma urea or creatinine and decreases in plasma potassium).

CONCLUSIONS:

Benazepril extended the useful life-span of dogs with ISACHC class II and III heart failure (due to CVD) and was well tolerated.

Abstract

Benazepril (BP), an angiotensin convertive enzyme inhibitor, was administered orally once daily for 4 weeks to 31 dogs with mild to moderate (NYHA functional classes II and III) congestive heart failure caused from mitral insufficiency (MI). There were no significant changes in clinical signs, electrocardiogram findings, radiographical observations and plasma biochemical results in 11 dogs treated with placebo for 4 weeks. In 31 dogs treated with BP, appetite increased, and mean scores of heart failure signs, such as activity, exercise tolerance, cough and respiratory effort, were significantly improved. No dog displays signs suggesting systemic hypotension. One dog died suddenly on the 26th day of treatment with BP. This dog had good vigor and appetite till the evening before the death, and cough and exercise tolerance had been gradually improving. The heart rate and ECG parameters of BP treated dogs did not change significantly, but length of long axis of the heart decreased. In plasma biochemical tests, plasma urea nitrogen (UN) levels did not change significantly, and plasma creatinine (CRE) levels increased slightly within the normal ranges during BP trial. Two dogs had higher plasma UN levels with slightly higher plasma CRE levels, but had normal general condition and other biochemical results. Plasma ACE activity decreased to 57.3% of pre-treatment level at 4 weeks after BP treatment. It is concluded that BP monotherapy was efficacious at least in dogs with relatively low grade congestive heart failure caused by MI.

Abstract

Forty dogs with mild to severe congestive heart failure (NYHA class II – IV) received benazepril at a dose of 0.406 (0.227-0.758) mg/kg body weight during 6 months. Furosemide and/or digoxin were added in some cases depending on the severity. By the end of the study 70% of the dogs had improved according to NYHA classification. Additionally exercise intolerance and cardiogenic cough had significantly improved. A decrease in heart rate was independent of digoxin administration and was independent of NYHA classification.

The study concluded that benazepril is a well tolerated and effective agent for the treatment of canine congestive heart failure

Abstract

Objectives

To test the tolerability of long-term administration of benazepril in dogs with congestive heart failure (CHF).

Methods

The study was a prospective, randomized, double-blinded, placebo-controlled clinical trial. A total of 162 dogs with New York Heart Association (NYHA) class II-IV heart failure caused by chronic valvular disease (CVD) or dilated cardiomyopathy (DCM) were enrolled. Benazepril (minimum dosage, 0.25 mg/kg) or placebo were administered orally once daily for up to 34 months. In this paper, we report results of plasma alanine aminotransferase (ALT), creatinine, potassium and urea.

Results

The two groups were matched at baseline (p≥0.18). Plasma creatinine concentrations were lower during treatment with benazepril versus placebo for all dogs (p=0.14) and every sub-group tested (NYHA II, III or IV; CVD; DCM; initial creatinine >124 μmol/L), although statistical significance was not reached (p=0.14–0.6). However, significantly (p=0.035) more cases of creatinine >124 μmol/L during treatment occurred with placebo (47%) as compared to benazepril (30%). Plasma ALT and urea values did not differ between groups for all dogs (p>0.5) or any sub-group (p=0.23–1.0). Plasma potassium values did not differ between groups for all dogs (p>0.5). Although differences approached statistical significance for potassium in some sub-groups (p=0.07–0.1), there were no consistent differences between groups.

Conclusions

Benazepril was well tolerated during long-term therapy in dogs with CHF and no specific precautions appear to be necessary regarding plasma ALT, creatinine, potassium or urea. The possible action of benazepril in improving renal function (evidenced via lower plasma creatinine) merits further investigation.

Abstract

The objective of the study was to test the effect of the angiotensin-converting enzyme inhibitor (ACEI) benazepril in cats with chronic kidney disease (CKD). A total of 192 cats with CKD with an initial plasma creatinine concentration > or = 2 mg/dL (> or = 177 micromol/L) and urine specific gravity < or = 1.025 were recruited into a double-blind, parallel-group, prospective, randomized clinical trial. Cats received daily (q24h) PO placebo (n = 96) or benazepril x HCl at a dosage of 0.5-1.0 mg/kg (n = 96) for up to 1,119 days. Most cats were fed exclusively a diet containing low amounts of phosphate, protein, and sodium. Benazepril produced a significant reduction in proteinuria, assessed by the urine protein-to-creatinine ratio (UPC, P = .005). This effect of benazepril was present in all subgroups tested, including cats with UPC <0.2, although the effect was largest in cats with higher UPCs. Plasma protein was maintained at higher concentrations with benazepril as compared with placebo during treatment in cats with initial UPC <1 (P = .038 versus P = .079 for all cats). There was no difference in renal survival time between the 2 groups when all 192 cats were compared. Mean +/- SD renal survival times were 637 +/- 480 days with benazepril and 520 +/- 323 days with placebo (P = .47). Mean +/- SD renal survival times in the 13 cats with initial UPC > or = 1 were 402 +/- 202 days with benazepril and 149 +/- 90 days with placebo (P = .27). Cats with initial UPC > or = 1 treated with benazepril had better appetite (P = .017) as compared with those treated with placebo. Benazepril was well tolerated. In conclusion, benazepril decreased proteinuria in cats with CKD.