Hot Literature: Spironolactone: A promising adjunctive therapy for myxomatous mitral valve disease

Human medicine has once again presented veterinarians with a possibility for improving the quality of life and survival times of many canine patients. Spironolactone, a selective aldosterone inhibitor, has been shown to decrease mortality in people with congestive heart failure. As heart failure progresses, aldosterone increases with the stimulation of several neurohormonal systems. These systems act to compensate for decreasing cardiac function. Aldosterone, however, increases extracellular fluid volume, putting increased strain on the heart. Additionally, it has a direct negative affect on the cardiac muscle and vasculature. In people, this long-term exposure to high aldosterone concentrations results in fibrosis-not a good thing in cases of cardiac disease.

Conventional treatments for heart failure include angiotensin-converting enzyme (ACE) inhibitors and furosemide. ACE inhibitors are poor suppressors of aldosterone secretion in both people and dogs. Furthermore, furosemide increases the aldosterone secretion. It was for these reasons that researchers in Europe conducted a double-blinded field study in dogs with naturally occurring myxomatous mitral valve disease (MMVD) to test the possible benefits of adding spironolactone therapy to conventional treatments.

More than 200 dogs were enrolled in the study, which consisted of two phases: a short-term evaluation including a two- and a three-month study, and a long-term evaluation (12-month study) that included dogs that had completed one of the short-term studies. At presentation, all of the dogs had moderate to severe mitral regurgitation caused by MMVD with an International Small Animal Cardiac Health Council classification of II or III. To participate, the dogs also had to be exhibiting a minimum of three clinical signs, including coughing, dyspnea, or syncope, and at least one behavioral sign such as decreased activity, decreased mobility, or altered demeanor.

The dogs were treated with conventional therapies, including an ACE inhibitor and furosemide. Treatment with digoxin or L-carnitine was also allowed. Veterinarians were permitted to adjust dosages as needed throughout the study. In addition to this therapy, spironolactone (2 mg/kg orally once a day) or placebo was added. Complete clinical evaluations were then performed on the dogs during the first week and at days 28, 56, and 84. For the long-term study, evaluations were continued at three-month intervals.

Results of the study were encouraging. For dogs treated with spironolactone, the 18-month survival rate was 84% compared with 66% in the control group. A primary endpoint (cardiac-related death, euthanasia, or severe worsening of mitral regurgitation) was reached in only 10.8% of patients receiving spironolactone compared with 25.5% of those given placebo. The results were even more exciting when considering only cardiac-related mortality, where there was a 69% reduction in the risk when an animal was treated with spironolactone.

This study was published in the Journal of Veterinary Internal Medicine earlier this year, and while it does not provide all of the answers to improving the quality and quantity of life for canine cardiac patients, it does offer some exciting new data to potentially improve the treatment of mitral regurgitation caused by MMVD.

Bernay F, Bland JM, Häggström J, et al. Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. J Vet Intern Med 2010;24(2):331-341.

Abstract available at http://www3.interscience.wiley.com/journal/123262185/abstract