Evaluation of benazepril in cats with heart disease in a prospective, randomized, blinded, placebo-controlled clinical trial.

BACKGROUND: Heart disease is an important cause of morbidity and mortality in cats, but there is limited evidence of the benefit of any medication. HYPOTHESIS: The angiotensin-converting enzyme inhibitor benazepril would delay the time to treatment failure in cats with heart disease of various etiologies. ANIMALS: One hundred fifty-one client-owned cats. METHODS: Cats with heart disease, confirmed by echocardiography, with or without clinical signs of congestive heart failure, were recruited between 2002 and 2005 and randomized to benazepril or placebo in a prospective, multicenter, parallel-group, blinded clinical trial. Benazepril (0.5-1.0 mg/kg) or placebo was administered PO once daily for up to 2 years. The primary endpoint was treatment failure. Analyses were conducted separately for all-cause treatment failure (main analysis) and heart disease-related treatment failure (supportive analysis). RESULTS: No benefit of benazepril versus placebo was detected for time to all-cause treatment failure (P = .42) or time to treatment failure related to heart disease (P = .21). Hazard ratios (95% confidence interval [CI]) from multivariate analysis for benazepril compared with placebo were 1.00 (0.57-1.74) for all-cause failure, and 0.99 (0.50-1.94) for forward selection and 0.93 (0.48-1.81) for bidirectional selection models for heart disease-related failure. There were no significant differences between groups over time after administration of the test articles in left atrium diameter, left ventricle wall thickness, quality of life scores, adverse events, or plasma biochemistry or hematology variables. CONCLUSIONS AND CLINICAL RELEVANCE: Benazepril was tolerated well in cats with heart disease, but no evidence of benefit was detected.

Repeated oral dose tolerance in dogs treated concomitantly with ciclosporin and oclacitinib for three weeks.

BACKGROUND: Ciclosporin and oclacitinib are immunomodulators approved for the treatment of canine atopic dermatitis. The administration of a short course of prednisolone at the beginning of ciclosporin therapy hastens the efficacy of this drug; oclacitinib has a rapid antipruritic effect similar to that of prednisolone. OBJECTIVES: To evaluate the oral tolerance of oclacitinib and ciclosporin given concurrently for three weeks. ANIMALS: Two groups of eight beagles. METHODS: Dogs were randomized to receive oclacitinib alone (0.4-0.6 mg/kg twice daily for 14 days then once daily for seven days) or in combination with ciclosporin (5 mg/kg once daily) for three weeks. They were examined every day and adverse events were recorded. Blood samples were collected during the acclimatization phase, weekly during treatment and at the end of the study for haematology, clinical chemistry and coagulation evaluation. RESULTS: There were no abnormal clinical observations following treatment with oclacitinib given alone or concomitantly with ciclosporin, with the exception of diarrhoea in two dogs receiving both drugs. Three dogs from each group experienced transient inappetence; three dogs treated with oclacitinib had mild weight loss. Clinical pathology parameters remained within the reference range for beagle dogs at that facility. CONCLUSIONS AND CLINICAL IMPORTANCE: The concomitant administration of ciclosporin and oclacitinib for three weeks to beagles was well tolerated and was not associated with an increase in the number of adverse events or laboratory abnormalities beyond those associated with oclacitinib given alone.

Efficacy of monepantel, derquantel and abamectin against adult stages of a multi-resistant Haemonchus contortus isolate.

Drug resistance in gastrointestinal nematodes is a severe problem for sheep farmers. With the recent introduction of monepantel (Zolvix®) and of derquantel plus abamectin (Startect®) in New Zealand, two new anthelmintic classes will be available to control gastrointestinal nematodes. While monepantel covers a broad spectrum of nematodes, the efficacy of derquantel is mid-spectrum and limited to a smaller number of species and stages. The combination of derquantel and abamectin allows to enlarge the spectrum and to cover most parasitic nematodes in sheep. However, the question remained open, if the efficacy of the new anthelmintics can be maintained in the presence of severe anthelmintic resistance. The present study investigated the efficacy against adult stages of a multi-resistant Haemonchus contortus isolate. While monepantel resulted in 100 % elimination, derquantel in combination with abamectin resulted in efficacies <95 % (faecal egg counts and worm counts).

Survival and echocardiographic data in dogs with congestive heart failure caused by mitral valve disease and treated by multiple drugs: a retrospective study of 21 cases.

This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.

Prognostic factors in cats with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. HYPOTHESIS: Some baseline variables are associated with shorter survival times in cats with CKD. ANIMALS: Client-owned cats. METHODS: Cats with CKD with initial plasma creatinine concentration > or =2.0 mg/dL and urine specific gravity (USG) < or = 1.025 were recruited into a prospective clinical trial that compared benazepril with a placebo. We describe baseline variables in 190 cats and their influence on renal survival time in the placebo group (95 cats), which was followed for up to 1,097 days. Renal survival time was defined as the time from initiation of therapy to the need for parenteral fluid therapy, euthanasia, or death related to renal failure. RESULTS: Of the 95 cats treated with a placebo, 58 were censored and 37 reached the renal survival end point (died, n = 0; euthanized, n = 17; parenteral fluids, n = 12; parenteral fluids followed by euthanasia, n = 8). Increased plasma creatinine concentration, increased urine protein-to-creatinine ratio (UPC), and increased blood leukocyte count were significantly (P < .01) associated with a shorter renal survival time and were independent risk factors. Increased concentrations of plasma phosphate or urea, and lower blood hemoglobin concentration or hematocrit were significantly (P < .01) associated with a shorter renal survival time and were dependent risk factors, because they also were significantly (P < .01) correlated with plasma creatinine concentration at baseline. CLINICAL IMPORTANCE: Several variables were significantly associated with a shorter renal survival time in cats with CKD.

Tolerability and efficacy of benazepril in cats with chronic kidney disease.

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.

Long-term tolerability of benazepril in dogs with congestive heart failure.

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 mumol/L), although statistical significance was not reached (p=0.14-0.6). However, significantly (p=0.035) more cases of creatinine >124 mumol/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.