Oral inhalation flecainide may help restore sinus rhythm in atrial fibrillation patients
Netherlands: A recent study in the journal Circulation: Arrhythmia and Electrophysiology found the administration of flecainide via oral inhalation to be safe and feasible for the conversion of recent-onset atrial fibrillation to sinus rhythm (SR). Also, it was potentially effective in acute care settings.
Currently, oral and intravenous flecainide is recommended for cardioversion of atrial fibrillation. Harry J G M Crijns, Maastricht University Medical Center and CARIM, Maastricht, the Netherlands, and colleagues aimed to evaluate the feasibility of delivering flecainide via oral inhalation (flecainide acetate inhalation solution) for acute conversion in an open-label, dose-escalation study. The researchers hypothesized that delivery of flecainide by oral inhalation would quickly reach plasma concentrations sufficient for restoring sinus rhythm in patients with recent-onset atrial fibrillation.
For this purpose, 101 patients with symptomatic atrial fibrillation (for ≤48 hours) were self administered flecainide acetate inhalation solution using a nebulizer (30 mg [n=10], 60 mg [n=22], 90 mg [n=21], 120 mg [n=19], and 120 mg in a formulation containing saccharin [n=29]). The researchers then obtained electrocardiograms and flecainide plasma concentrations, 4-hour Holter was used to monitoring cardiac rhythm, and adverse events were recorded.
The key findings of the study were as follows:
- Conversion rates increased with dose and with the maximum plasma concentrations of flecainide.
- At the highest dose, 48% of patients converted to sinus rhythm within 90 minutes from the start of inhalation.
- Among patients who achieved a maximum plasma concentration >200 ng/mL, the conversion rate within 90 minutes was 50%; for those who achieved a maximum plasma concentration <200 ng/mL, it was 24%.
- The conversion was rapid (median time to conversion of 8.1 minutes from the end of inhalation), and conversion led to symptom resolution in 86% of the responders.
- Adverse events were typically mild and transient and included: cough, throat pain, throat irritation; at the highest dose with the formulation containing saccharin, these adverse events were reported by 41%, 14%, and 3% of patients, respectively.
- Cardiac adverse events consistent with those observed with oral and intravenous flecainide were uncommon and included post-conversion pauses (n=2), bradycardia (n=1), and atrial flutter with 1:1 atrioventricular conduction (n=1); none required treatment, and all resolved without sequelae.
The researchers conclude, "administration of flecainide via oral inhalation was shown to be safe and to yield plasma concentrations of flecainide sufficient to restore sinus rhythm in patients with recent-onset atrial fibrillation."
Reference:
Crijns HJGM, Elvan A, Al-Windy N, Tuininga YS, Badings E, Aksoy I, Van Gelder IC, Madhavapeddi P, Camm AJ, Kowey PR, Ruskin JN, Belardinelli L; INSTANT Investigators. Open-Label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution for Acute Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm. Circ Arrhythm Electrophysiol. 2022 Feb 24:CIRCEP121010204. doi: 10.1161/CIRCEP.121.010204. Epub ahead of print. PMID: 35196871.
KEYWORDS: Circulation, flecainide acetate, atrial fibrillation, sinus rhythm, cardioversion, American Heart Association, oral inhalation, Harry J G M Crijns, recent-onset atrial fibrillation
