Orally inhaled flecainide favorable for conversion of atrial fibrillation to sinus rhythm: Insights from INSTANT phase 2 trial

INSTANT was an open-label, multicenter, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation to sinus rhythm.

The researchers reported that the risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable; suggesting that FlecIH could provide an effective, safe, and convenient first-line therapeutic option.

Atrial fibrillation is characterized by irregular and often rapid heart rate and poses substantial risks of stroke, heart failure, and other cardiovascular complications. While several pharmacological and interventional strategies exist for managing AF, achieving and maintaining sinus rhythm remains a cornerstone of therapy to mitigate associated morbidity and mortality.

Atrial fibrillation stands as one of the most prevalent cardiac arrhythmias worldwide, with its management presenting a significant challenge in clinical practice. Amidst this backdrop, the emerging use of orally inhaled flecainide offers a beacon of hope for restoring sinus rhythm in patients with AF.

Against the above background, Jeremy N. Ruskin, Cardiac Arrhythmia Service GRB 8, Massachusetts General Hospital, Boston, Massachusetts, USA, and colleagues aimed to investigate the safety and efficacy in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. The mean age of the patients was 60.5 years, the mean body mass index was 27.0 kg/m2, and 34.7% were women.

Patients self-administered flecainide acetate oral inhalation solution over 8 minutes, using a breath-actuated nebulizer, in a supervised medical setting and were continuously monitored for 90 minutes using a 12-lead Holter.

The researchers reported the following findings:

· All patients had ≥1 AF-related symptom at baseline, and 87.8% had AF symptoms for ≤24 hours.

· The conversion rate was 42.6% with a median time to conversion of 14.6 minutes.

· The conversion rate was 46.9% in a subpopulation that excluded predose flecainide exposure for the current AF episode.

· Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5.

· In the conversion-no group, 81.5% of patients underwent electrical cardioversion by day 5.

· The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration.

In conclusion, the risk-benefit of orally inhaled flecainide acetate for acute cardioversion of recent-onset AF is favorable and could provide an effective, safe, and convenient first-line therapeutic option for the conversion of recent-onset AF.

"The delivery of flecainide by oral inhalation in the hospital/ED setting holds the potential to provide a rapid and practical treatment, reducing rates of hospitalization and health care costs," the researchers wrote. "There is a need for further studies to confirm the current study findings on the clinical effectiveness and safety of inhaled flecainide."

Reference:

Ruskin JN, Camm AJ, Dufton C, Woite-Silva AC, Tuininga Y, Badings E, De Jong JSSG, Oosterhof T, Aksoy I, Kuijper AFM, Van Gelder IC, van Dijk V, Nuyens D, Schellings D, Lee MY, Kowey PR, Crijns HJGM, Maupas J, Belardinelli L; INSTANT Investigators. Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial. JACC Clin Electrophysiol. 2024 Mar 26:S2405-500X(24)00164-6. doi: 10.1016/j.jacep.2024.02.021. Epub ahead of print. PMID: 38613545.