AP30663 at a dose of 5 mg/kg achieved a 55% cardioversion rate within 90 minutes compared to 0% with placebo in patients with recent-onset atrial fibrillation.
RCT (n=66)
Double-blind
Computer-generated random sequence
Yes
Does AP30663 improve cardioversion to sinus rhythm in patients with recent-onset atrial fibrillation?
AP30663, a novel KCa2 channel inhibitor, effectively cardioverts recent-onset atrial fibrillation to sinus rhythm without inducing ventricular arrhythmias, representing a promising new mechanism for rhythm control.
Effect estimate: posterior probability of superiority >99.9%
Absolute Event Rate: 55% vs 0%
Absolute Risk Reduction: 55%
Abstract Existing antiarrhythmic drugs to treat atrial fibrillation (AF) have incomplete efficacy, contraindications and adverse effects, including proarrhythmia. AP30663, an inhibitor of the K Ca 2 channel, has demonstrated AF efficacy in animals; however, its efficacy in humans with AF is unknown. Here we conducted a phase 2 trial in which patients with a current episode of AF lasting for 7 days or less were randomized to receive an intravenous infusion of 3 or 5 mg kg −1 AP30663 or placebo. The trial was prematurely discontinued because of slow enrollment during the coronavirus disease 2019 pandemic. The primary endpoint of the trial was cardioversion from AF to sinus rhythm within 90 min from the start of the infusion, analyzed with Bayesian statistics. Among 59 patients randomized and included in the efficacy analyses, the primary endpoint occurred in 42% (5 of 12), 55% (12 of 22) and 0% (0 of 25) of patients treated with 3 mg kg −1 AP30663, 5 mg kg −1 AP30663 or placebo, respectively. Both doses demonstrated more than 99.9% probability of superiority over placebo, surpassing the prespecified 95% threshold. The mean time to cardioversion, a secondary endpoint, was 47 (s.d. = 23) and 41 (s.d. = 24) minutes for 3 mg kg −1 and 5 mg kg −1 AP30663, respectively. AP30663 caused a transient increase in the QTcF interval, with a maximum mean effect of 37.7 ms for the 5 mg kg −1 dose. For both dose groups, no ventricular arrhythmias occurred and adverse event rates were comparable to the placebo group. AP30663 demonstrated AF cardioversion efficacy in patients with recent-onset AF episodes. K Ca 2 channel inhibition may be an attractive mechanism for rhythm control of AF that should be studied further in randomized trials. ClinicalTrials.gov registration: NCT04571385 .
Holst et al. (Wed,) conducted a rct in Atrial fibrillation (n=66). AP30663 vs. Placebo was evaluated on Cardioversion from AF to sinus rhythm within 90 min from the start of the infusion (posterior probability of superiority >99.9%). AP30663 at a dose of 5 mg/kg achieved a 55% cardioversion rate within 90 minutes compared to 0% with placebo in patients with recent-onset atrial fibrillation.