2046: Using a Novel Combination of Drugs to Treat Arrhythmia and Heart Failure in Dogs

Grant Status: Closed

Grant Amount: $33,060
Janice McIntosh Bright, DVM, BSN; Colorado State University
January 1, 2014 - June 30, 2018
Sponsor(s): American Cavalier King Charles Spaniel Club Charitable Trust, Chihuahua Club of America, Saluki Health Research, Inc., Irish Wolfhound Club of America, Inc., Staffordshire Terrier Club of America
Breed(s): -All Dogs
Research Program Area: Cardiology

Abstract

Atrial fibrillation is a common heart rhythm abnormality (arrhythmia) in dogs. This arrhythmia affects all dog breeds and frequently coexists with heart failure causing worsening of disease and high mortality. Atrial fibrillation may be managed by administering drugs to slow heart rate or by restoring normal rhythm (cardioversion). Dr. Bright will evaluate dogs with naturally occurring atrial fibrillation and heart failure for their responsiveness to two drugs -- amidodarone, an antiarrhythmic agent, and ranolazine, a drug used in humans with coronary heart disease. She will determine whether ranolazine given with amiodarone prolongs normal rhythm compared to amiodarone alone and whether ranolazine also improves heart function. Results will validate combined ranolazine/amiodarone administration as an improved new treatment for atrial fibrillation in dogs with heart failure, extending their quality of life.


Project Summary

Atrial fibrillation (AF) is a common heart rhythm abnormality (arrhythmia) that affects all breeds of dogs and frequently coexists with heart failure (HF) resulting in worsening of HF and high mortality. AF may be managed by administering drugs to slow heart rate or by restoring normal rhythm (cardioversion). Slowing rate often does not provide adequate relief and may accelerate progression of HF. Cardioversion safely restores normal rhythm and mitigates HF in >80% of affected dogs. However, owners often decline cardioversion because of possible relapse of AF despite routine use of the antiarrhythmic agent, amiodarone. Ranolazine is a pharmaceutical agent used in people with coronary heart disease; however, this drug has significant anti-AF effects. Combined administration of ranolazine and amiodarone provides greater suppression of AF in humans and research dogs than either drug alone. Ranolazine also improves contraction of heart muscle in dogs with experimental HF. This project is a randomized, placebo controlled clinical trial to determine whether ranolazine, given with amiodarone, prolongs normal rhythm after cardioversion compared to amiodarone alone and whether ranolazine also improves heart function. 22 dogs were enrolled in the trial after restoration of normal heart rhythm, and all 22 reached the study endpoint. Eleven dogs received conventional antiarrhythmic treatment (amiodarone plus placebo) and 11 received ranolazine (in addition to amiodarone). Analysis of plasma from dogs treated with ranolazine confirmed therapeutic drug concentrations in all dogs in the treatment group. Duration of normal rhythm and echodardiographic measurements of cardiac function were compared between treatment groups. Unfortunately, statistical analyses showed no beneficial effect of ranolazine compared to conventional treatment with amiodarone.

Publication(s)

None at this time.

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