Flecainide Safety in Patients With Coronary Artery Disease and Atrial Fibrillation

The primary outcome measure is a composite safety outcome including all-cause mortality, severe adverse events leading to drug discontinuation, and unscheduled hospitalisation for heart failure or acute coronary syndrome. Each of these individual components is assessed as secondary outcome.

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.