Reduced Ventricular Proarrhythmic Potential of the Novel Combined Ion-Channel Blocker AZD1305 Versus Dofetilide in Dogs With Remodeled Hearts
Key result
AZD1305 induced torsades de pointes in only 36.4% (4 of 11) of dogs with remodeled hearts, compared to 100% (14 of 14) treated with dofetilide, indicating lower proarrhythmic potential.
Why the study?
Does AZD1305 reduce proarrhythmic potential compared to dofetilide in dogs with remodeled hearts?
Population
Anesthetized mongrel dogs with chronic complete atrioventricular block and myocardial hypertrophic remodeling
Comparison
AZD1305 (combined ion-channel blocker) vs Dofetilide (selective I(Kr) blocker)
Design
Preclinical
Follow-up
>2 weeks after induction of atrioventricular block
Authors
Discussion
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Member takes
Implication
May support AZD1305 development as lower-risk antiarrhythmic; leaves open translation to human use.
Structured PICO
Does AZD1305 reduce proarrhythmic potential compared to dofetilide in dogs with remodeled hearts?
P
Population
14 mongrel dogs with chronic complete atrioventricular block and myocardial hypertrophic remodeling.
I
Intervention
AZD1305 (combined ion-channel blocker)
C
Comparator
Dofetilide (selective I(Kr) blocker)
O
Outcome
Electrophysiological parameters (QT and RR intervals) and susceptibility to acquired torsades de pointessafety
Main Result
Absolute Event Rate: 36.4% vs 100%
AZD1305 induces less repolarization instability and has a lower ventricular proarrhythmic potential than dofetilide in a canine model of remodeled hearts.
Cite This Study
Johnson et al. (2011) studied Chronic complete atrioventricular block and myocardial hypertrophic remodeling (n=14). AZD1305 vs. Dofetilide was evaluated on Torsades de pointes induction. AZD1305 induced torsades de pointes in only 36.4% (4 of 11) of dogs with remodeled hearts, compared to 100% (14 of 14) treated with dofetilide, indicating lower proarrhythmic potential.