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Benazepril and survival in dogs with congestive heart failure

Clinical Scenario

Clive is a 10 year old, male neutered terrier cross who belongs to an elderly client of your practice, Mr Edwards. He presented two days ago in congestive heart failure (CHF), and you have now stabilised him and established that the CHF is due to mitral and tricuspid degenerative valve disease. Mr Edwards is very attached to Clive and wants to do what is best for him, but has a very limited budget and is worried about being able to administer medication. Clive clearly needs frusemide but you wonder, in light of the financial situation, what the survival benefits of using benazepril as well are.....

3-Part Question (PICO)

In [dogs in congestive heart failure secondary to valvular disease] does [benazepril in combination with standard therapy compared to placebo plus standard therapy] improve [survival]?

Search Strategy and Summary of Evidence

Search Strategy

MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) 1946 to Present using the OVID interface

(dog.mp. OR dogs.mp. OR canine.mp. OR canines.mp. OR canis.mp. OR exp Dogs/)

AND

(heart failure.mp. OR heart insufficienc$.mp. OR heart disease$.mp. OR cardiac failure.mp. OR cardiac insufficienc$.mp. OR cardiac disease$.mp. OR CHF.mp. OR exp Heart Failure/ OR exp Heart Diseases/)

AND

(benazepril.mp. OR ACE inhibitor.mp. OR ACE inhibitors.mp. OR angiotensin converting enzyme inhibitor.mp. OR angiotensin converting enzyme inhibitors.mp. OR ACEI.mp. OR ACEi.mp. OR ACE-I.mp. OR ACE-i.mp. OR exp Angiotensin-Converting Enzyme Inhibitors/)

CAB Abstracts 1910 to Present using the OVID interface

(dog.mp. OR dogs.mp. OR canine.mp. OR canines.mp. OR canis.mp. OR exp dogs/)

AND

(heart failure.mp. OR heart insufficienc$.mp. OR heart disease$.mp. OR cardiac failure.mp. OR cardiac insufficienc$.mp. OR cardiac disease$.mp. OR CHF.mp. OR exp heart diseases/ OR exp cardiac insufficiency/)

AND

(benazepril.mp. OR ACE inhibitor.mp. OR ACE inhibitors.mp. OR angiotensin converting enzyme inhibitor.mp. OR angiotensin converting enzyme inhibitors.mp. OR ACEI.mp. OR ACEi.mp. OR ACE-I.mp. OR ACE-i.mp.)

Search Outcome

MEDLINE

  • 396 papers found in MEDLINE search
  • 393 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 2 papers excluded as they are review articles/in vitro research/conference proceedings
  • 1 total relevant papers from MEDLINE

CAB Abstracts

  • 118 papers found in CAB search
  • 109 papers excluded as they don't meet the PICO question
  • 1 papers excluded as they are in a foreign language
  • 7 papers excluded as they are review articles/in vitro research/conference proceedings
  • 1 total relevant papers from CAB

Total relevant papers

1 relevant papers from both MEDLINE and CAB Abstracts

Summary of Evidence

The BENCH Study Group (1999) Europe (multicentre)

Title: The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial.
Patient group: 162 Dogs in ISACHC Class II and III Heart failure due to chronic valvular disease (CVD) or dilated cardiomyopathy (DCM)
Study Type: Randomised controlled trial
Outcomes:
  • Survival time (primary outcome)
  • Time to worsening of heart failure from ISACHC class II to class III
  • Exercise tolerance
  • Global clinical condition
  • Tolerability of treatments
Key Results:
  • Overall, dogs in the benazepril group survived significantly longer than those in the placebo group (428+/-52 days in the benazepril group versus 158+/-17 days in the placebo group, p=0.019)
  • There was a significant increase in survival time in the benazepril group compared to placebo in dogs suffering from CVD (436+/-57 days versus 151+/-20 days, p=0.015)
  • There was no difference in survival time between the treatment groups for dogs in the DCM subgroup (p=0.66)
  • Overall, 20 out of 87 dogs died in the benazepril group and 19 out of 75 in the placebo group from reasons relating to heart failure
  • Benazepril  delayed the worsening of heart failure class II to class III by a factor of 2 (394 days in the benazepril group versus 209 days in the placebo group, p<0.05)
  • Exercise tolerance and global clinical condition were significantly improved in dogs in the benazepril group compared to the placebo group at day 28 (p<0.05), but there were no differences between the 2 groups at day 7 or 56
Study Weaknesses:
  • Previous use of diuretics was more frequent in the placebo group compared to the benazepril group (61% versus 47%) - no statistical significance value of this figure given
  • Small number of dogs per group for all subgroup analyses
  • No sample size justification
  • Large withdrawal rate from the study, leading to a small final sample size for survival analysis
  • Statistical significance values not reported in all data tables or for all data comparisons
Attachment:
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Comments

In general this was a well conducted clinical trial which suffered from a large withdrawal rate and lack of sample size justification. The large withdrawal rate means that the survival analysis at the end of the study was based on a small sample size, making the results potentially unreliable. There was a large number of 'adverse events' reported in the trial (which included cardiac events), although the occurrence of these did not differ between the benazepril and placebo groups.

The dogs were on a number of additional therapies, but none of the dogs in the study received pimobendan.

Bottom line

Benazepril increases the survival time of dogs in congestive heart failure secondary to chronic valvular disease.

Disclaimer

The BETs on this website are a summary of the evidence found on a topic and are not clinical guidelines. It is the responsibility of the individual veterinary surgeon to ensure appropriate decisions are made based on the specific circumstances of patients under their care, taking into account other factors such as local licensing regulations. Read small print

References

The BENCH (BENazepril in Canine Heart disease) Study Group (1999) The effect of benazepril on survival times and clinical signs of dogs with congestive heart failure: results of a multicenter, prospective, randomized, double-blinded, placebo-controlled, long-term clinical trial. Journal of Veterinary Cardiology 1: 7-18.

About this BET

First author:
Kathryn Wareham
Second author:
Rachel Dean
Institution:
CEVM, University of Nottingham
Search last performed:
2015-02-23 12:40:11
Original publication date:
2015-02-27 12:40:11
Last updated:
2015-02-27 12:40:11
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