Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease.
BACKGROUND
Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies.


OBJECTIVE
Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD).


METHODS
Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]).


METHODS
Double-blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac-related death, euthanasia, or severe worsening of MR.


RESULTS
Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22-0.90; log rank test, P = .017). Risk of cardiac-related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13-0.76; P = .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110).


CONCLUSIONS
Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.
Bernay
F
F
R&D Department, Ceva Santé Animale, Libourne, France. florence.bernay@ceva.com
Bland
J M
JM
Häggström
J
J
Baduel
L
L
Combes
B
B
Lopez
A
A
Kaltsatos
V
V
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004077:Digoxin / Q000008:administration & dosage / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008944:Mitral Valve Insufficiency / Q000188:drug therapy / Q000662:veterinary*; D016016:Proportional Hazards Models; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D004232:Diuretics; D013148:Spironolactone; D004077:Digoxin; D005665:Furosemide