Peer-reviewed veterinary case report
New heart rhythm drug AZD1305 safer than dofetilide in dogs
By Johnson, Daniel M et al.·Published in Circulation. Arrhythmia and electrophysiology·2012·Department of Cardiology, Netherlands·View original on PubMed →
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Original publication title: Reduced ventricular proarrhythmic potential of the novel combined ion-channel blocker AZD1305 versus dofetilide in dogs with remodeled hearts.
- Species:
- dog
Plain-English summary
A group of dogs with heart issues, specifically chronic complete atrioventricular block, were given a new medication called AZD1305 to see how it compared to an existing drug, dofetilide, in managing their heart rhythm. While both medications caused similar delays in heart repolarization, AZD1305 led to fewer instances of dangerous heart arrhythmias known as torsades de pointes. This suggests that AZD1305 may be a safer option for dogs with remodeled hearts. Overall, the dogs showed a better response to AZD1305 with less risk of serious heart problems.
People also search for: dog heart arrhythmia treatment · AZD1305 for dogs · dofetilide side effects in dogs
Abstract
BACKGROUND: AZD1305 is an investigational antiarrhythmic agent for management of atrial fibrillation. It blocks various cardiac ion currents at different potencies and has atrial-predominant electrophysiological effects. We investigated the electrophysiological and proarrhythmic effects of AZD1305 versus dofetilide in dogs with chronic complete atrioventricular block and myocardial hypertrophic remodeling. METHODS AND RESULTS: AZD1305 was administered to anesthetized mongrel dogs before and >2 weeks after the induction of atrioventricular block and ventricular and atrial electrophysiological parameters were assessed. In all dogs, the selective I(Kr) blocker dofetilide was used to examine susceptibility to acquired torsades de pointes in chronic atrioventricular block and for comparison. At normal sinus rhythm, AZD1305 increased QT and RR intervals from 290±7 to 397±15 ms (+37%, P<0.0001) and from 603±22 to 778±32 ms (+29%, P=0.002), respectively. In the same animals at chronic atrioventricular block, AZD1305 increased the QT interval from 535±28 to 747±36 ms (+40%, P<0.0001), similar to the QT prolongation by dofetilide (511±22 to 703±45 ms [+38%, P<0.0001]). AZD1305 slightly slowed the idioventricular rhythm. Whereas all (n=14) chronic atrioventricular block animals exhibited torsades de pointes on dofetilide, the arrhythmia was induced in only 4 of 11 dogs after AZD1305. Beat-to-beat variability of left-ventricular monophasic-action-potential duration increased after dofetilide (2.3±0.2 to 6.3±0.7 ms; P<0.0001) but not after AZD1305 (2.8±0.3 to 3.7±0.3 ms; P=0.20) despite similar left-ventricular monophasic-action-potential duration prolongations. CONCLUSIONS: Despite causing similar degrees of repolarization delay as the selective I(Kr) blocker dofetilide, the combined ion-channel blocker AZD1305 induces less repolarization instability and has a lower ventricular proarrhythmic potential in the remodeled dog heart.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/22080293/