Mp-453091-1 effect of etripamil nasal spray on ventricular rate in patients experiencing symptomatic atrial fibrillation

Atrial fibrillation (AF) is often associated with symptomatically rapid ventricular rates (RVR), for which there is no rapid-onset, at-home treatment approved. Intranasally self-administered etripamil is a calcium channel blocker that has rapid-onset of action and prolongs refractoriness in the AV-node. To determine whether etripamil is safe and effective in acutely reducing RVR in patients with electrocardiographically (ECG) documented AF. NODE-303 is an open-label study evaluating self-administered etripamil, by patients with symptomatic recurrent episodes of paroxysmal supraventricular tachycardia (PSVT). Continuous ECGs were acquired at the onset of symptoms and patients annotated time of drug receipt (70 mg) on the recording. Central examination of ECG data showed that 26 (n=21 patients) of 1024 episodes of treated perceived PSVT involved AF with RVR rather than PSVT. Differences between initial VR and VR at 1-min following intervals were calculated for each episode over the 60 min post drug receipt. VR data after a conversion to sinus rhythm (SR) were excluded. The differences at each timepoint were averaged and are reported and plotted as a delta ± standard error of the mean (SEM) (Fig. 1). Twenty-one AF episodes had sufficiently interpretable ECG data and were analyzed. At baseline, defined as the start of ECG recording, mean VR ± SEM = 129.7 ± 5.4 bpm. Of the 21 AF episodes, 17 had a VR ≥110 bpm at baseline, mean VR ± SEM =138.3 ± 4.3 bpm. The time of drug receipt was estimated to be at start of ECG recording in 12 of 21 episodes. Six episodes converted to SR during the 60 min window, without conversion pauses >2 sec. Averaged reductions in VR from baseline (deltas) were observed throughout the 60-min window, maximally (-27.4 ± 6.1 bpm) at 22 min, and -16.2 bpm ± 5.6 at 60 min (Fig. 1). The upper bound of the SEM did not traverse the baseline over the 60-min. Etripamil was well-tolerated and there were no serious adverse events. In patients with AF and RVR, etripamil, self-administered as prompted by symptoms, resulted in a reduction in VR that was sustained over 60 min, with a timing aligned with the known timing of pharmacologic action of etripamil. No safety problems were observed with administration of etripamil in AF in this data set. These findings warrant further study and suggest a potential role for the drug for acute control of RVR in patients with AF.