Analytical Clinical Studies
Preliminary investigation of orally administered benazepril in
horses with left-sided valvular regurgitation
, S. GIGU
* , S. A. BROWN
, M. H. BARTON
, G. RAPOPORT
, M. BARBA
, K. A. DEMBEK
R. E. TORIBIO
and A. E. COLEMAN
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
*Correspondence email: email@example.com. Dr M. Barba’s present address is: Departmento de Medicina y Cirug
ıa Animal, Facultad de Veterinaria,
Universidad Cardenal Herrera – CEU, CEU Universities, Valencia, Spain. Received: 11.04.17; Accepted: 11.10.17
Background: Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses
with valvular regurgitation.
Objective: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation.
Study design: Prospective, randomised double-blind, placebo-controlled trial.
Methods: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a
placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum
ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7
and 28 days of treatment.
Results: Relative to baseline, horses treated with benazepril had statistically signiﬁcant reduction in left ventricular internal diameter in systole (mean
difference between groups = À0.97 cm; 95% CI = À1.5 to À0.43 cm), aortic sinus diameter (À0.31 cm; À0.54 to À0.07 cm), and percentage of the
aortic annulus diameter occupied by the base of the AR jet (À17.05%; À31.17 to À2.93%) compared with horses receiving a placebo. In addition, horses
treated with benazepril had a signiﬁcantly greater increase in cardiac output (11.95 L/min; 1.17–22.73 L/min) and fractional shortening (7.59%; 3.3–
11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and
aldosterone were not signiﬁcantly different between treatment groups or among time points.
Main limitations: Very small sample size and short treatment period.
Conclusions: Treatment with oral benazepril resulted in statistically signiﬁcant echocardiographic changes that might indicate reduced cardiac
afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of
benazepril is beneﬁcial in horses with valvular regurgitation.
The Summary is available in Spanish – see Supporting Information
Keywords: horse; ACE inhibitors; mitral regurgitation; aortic regurgitation
Activation of the renin-angiotensin-aldosterone system (RAAS) and its
deleterious effects are well recognised in people with valvular regurgitation
often accomplished by the administration of angiotensin-converting
enzyme (ACE) inhibitors, has become part of the standard of care both in
human and small animal patients diagnosed with CHF [2,3]. ACE inhibitors
improve quality of life and extend survival times in dogs with CHF resulting
from myxomatous mitral valve regurgitation (MR) [4–6]. In addition, ACE
inhibitors have been shown to improve ventricular function and reduce the
severity of MR or aortic valve regurgitation (AR) in human patients with
chronic valvular disease even in the absence of CHF [7,8].
Activation of the RAAS also occurs in horses with valvular regurgitation
. Despite lack of data regarding their efﬁcacy, ACE inhibitors have been
recommended for the treatment of horses with severe valvular diseases.
Enalapril given orally has low bioavailability in horses and does not block
ACE effectively [10,11]. Quinapril given orally to horses with MR increased
stroke volume and cardiac output (CO), and decreased MR velocity time
integral . However, the lack of an untreated control group in the
aforementioned study precluded differentiation of a true effect of quinapril
from that resulting from natural changes in haemodynamics over time. In
healthy horses, oral benazepril at a dose of 0.5 mg/kg more effectively
inhibited serum ACE activity than did quinapril, perindopril or ramipril .
Similarly, oral benazepril at the same dose was more effective at
attenuating exercise-induced hypertension than enalapril, quinapril or
ramipril . More recently, oral benazepril at a dose of 1 mg/kg was
superior to a dose of 0.5 mg/kg at attenuating the rise in blood pressure
after administration of exogenous angiotensin I, whereas administration of
higher dosages did not provide additional beneﬁt .
The objectives of this study were to evaluate the echocardiographic and
hormonal changes in response to oral benazepril in horses with MR and/or
AR. Our hypotheses were that treatment of affected horses with benazepril
would improve echocardiographic variables and result in blockade of the
RAAS throughout the study period, when compared to treatment with a
Materials and methods
The medical records of horses admitted to the University of Georgia and
Auburn University between September 2010 and June 2015 were reviewed
for the presence of MR and/or AR diagnosed based on characteristic
murmurs and echocardiographic examination. The cardiology reports from
the most recent hospital visits were reviewed and horses were selected
for inclusion if the left atrium (LA) was ≥13 cm in diameter at the end of
Equine Veterinary Journal 50 (2018) 446–451 © 2017 EVJ Ltd
Equine Veterinary Journal ISSN 0425-1644