Flecainide Safety in Patients With Coronary Artery Disease and Atrial Fibrillation

Death from any cause

Any severe AE leading to intervention discontinuation, including bradyarrhythmias, ventricular arrhythmias, atrial flutter with 1:1 conduction, QT/QRS prolongation, serious extra-cardiac adverse events

Unscheduled hospitalisation for heart failure or acute coronary syndrome

Freedom from fast atrial arrhythmia post-treatment (clinical recurrence of AF)

Composite of cardiovascular death, myocardial infarction, stroke

Incidence of catheter ablation for AF during follow-up

Total number of days of cardiovascular hospitalisation

All serious adverse events and adverse events:

• Frequency and severity of all treatment-emergent adverse events
• Proportion of participants experiencing at least one AE/SAE.
• Specific drug-related adverse events (e.g., QT prolongation, proarrhythmia, bradycardia, hypotension, fatigue, gastrointestinal disturbances).

Changes in cardiac function assessed by left ventricular ejection fraction expressed in percentages (%) from baseline measured by echocardiography

Change in N-terminal-pro-brain Natriuretic Peptide (NT-proBNP) at 3 months from baseline

Change in QTc interval (ms) and QRS duration (ms) from baseline

Total within-trial healthcare resource utilization expressed in Euro (€)

Change in patient reported outcomes assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. The AFEQT questionnaire is a 20-item, disease-specific, patient-reported outcome measure ranging from 0 to 100 with a higher value corresponding to a better quality of life.

Change in patient-reported outcome as assessed by the EuroQoL-5 dimension health utility index (EQ-5D-5L) questionnaire. The EQ-5D-5L measures health-related quality of life across five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) on five severity levels (1=no problem to 5=extreme problem). Results are interpreted via a 5-digit health state profile (e.g., 11211), a calculated utility index (ranging from <0 to 1, where 1=full health), and a 0-100 Visual Analog Scale (VAS). A higher score corresponds to a better quality of life.

Change in patient-reported outcome as assessed by the Short Form-12 (SF-12) health survey. The Short Form-12 (SF-12) health survey is interpreted by calculating two main, norm-based scores-the Physical Component Summary (PCS) and Mental Component Summary (MCS)-where a score of 50 represents the average for the general population. Scores above 50 indicate better-than-average health-related quality of life, while scores below 50 indicate below-average health.

Change in patient-reported outcome as assessed by the European Heart Rhythm Association (EHRA) symptom score. The EHRA symptom score is a standardized, four-level classification system used to quantify the severity of symptoms in patients with atrial fibrillation based on how they impact daily activities.

EHRA Symptom Score Classification (I-IV):

EHRA I (Asymptomatic): No symptoms are experienced. EHRA II (Mild Symptoms): Normal daily activity is not affected. EHRA III (Severe Symptoms): Normal daily activity is affected. EHRA IV (Disabling Symptoms): Normal daily activity is discontinued.

Change in patient-reported outcome as assessed by the Work Productivity and Activity Impairment (WPAI) questionnaire. The WPAI questionnaire is interpreted by calculating four key impairment percentages over the past 7 days, with higher scores (0-100%) indicating greater impairment and lower productivity. It measures absenteeism (time missed), presenteeism (impairment while working), overall work loss, and daily activity impairment, using a 0-10 scale for productivity.