Flecainide
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Flecainide: From Atrial Fibrillation to Stroke Disorder
One-Sentence Summary
Flecainide is a class 1C sodium channel blocker originally used to control atrial fibrillation and other arrhythmias. The TxGNN model predicts it may be useful for stroke disorder, but the link is indirect: 1 Phase 3 clinical trial tests arrhythmia prevention after PFO closure rather than stroke itself, and the literature is mostly about atrial fibrillation management.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atrial fibrillation |
| Predicted New Indication | Stroke disorder |
| TxGNN Prediction Score | 99.91% |
| Evidence Level | L3 |
| New Zealand Market Status | Cancelled only (no currently valid authorizations) |
| Number of Authorizations | 6 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known information, flecainide is a class 1C antiarrhythmic that blocks cardiac sodium channels. Its efficacy in atrial fibrillation is established, and it is used for rhythm control.
Atrial fibrillation is a major cause of cardioembolic stroke. Any benefit for stroke would therefore come from reducing arrhythmia burden, not from a direct neuroprotective or antithrombotic effect. The only Phase 3 trial tests flecainide for preventing atrial arrhythmia after closure of a patent foramen ovale (PFO), a procedure done to prevent recurrent cryptogenic stroke. That is a post-procedural complication, not stroke itself.
The very high TxGNN score most likely reflects the well-known atrial fibrillation–stroke association in the knowledge graph rather than independent evidence of benefit. The prediction should be treated as a research question.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05213104 | Phase 3 | Active, not recruiting | 186 | Flecainide to lower the risk of atrial arrhythmia or tachycardia after PFO closure. The primary endpoint is arrhythmia, not stroke recurrence, so it supports stroke care only indirectly. No results yet; completion expected September 2026. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38702961 | 2024 | Secondary analysis of RCT | Europace | Safety and efficacy of long-term sodium channel blocker (flecainide, propafenone) therapy for early rhythm control in EAST-AFNET 4 |
| 38551548 | 2024 | Cohort/Meta-analysis | JACC Clin Electrophysiol | Class 1C antiarrhythmics for PVC suppression in nonischemic cardiomyopathy with ICDs |
| 41954064 | 2026 | Cohort | J Am Heart Assoc | Long-term outcomes of class 1C drugs in atrial fibrillation; benefit over rate control is still unclear |
| 37109225 | 2023 | RCT (pilot, open-label) | J Clin Med | Carvedilol vs flecainide for idiopathic outflow tract PVCs |
| 25820938 | 2015 | Systematic review (Cochrane) | Cochrane Database Syst Rev | Antiarrhythmics for maintaining sinus rhythm after cardioversion of atrial fibrillation |
| 41152878 | 2025 | Cohort | BMC Med | Stroke and bleeding risk with concomitant DOAC and interacting antiarrhythmic use in non-valvular AF |
| 25430048 | 2014 | Review | BMJ Clin Evid | Acute-onset atrial fibrillation increases stroke and heart failure risk |
| 30067936 | 2018 | Guideline | Med J Aust | Australian and New Zealand clinical guidelines for atrial fibrillation diagnosis and management |
| 8729366 | 1995 | Clinical study | Arch Mal Coeur Vaiss | Atrial electrophysiological study with intravenous flecainide in 38 patients with unexplained ischaemic cerebrovascular events |
| 27884575 | 2017 | Case report | J Emerg Med | Brugada pattern unmasked by flecainide overdose, a proarrhythmic safety signal |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2694956 | Almarytm | Inj 10 mg per ml, 15 ml ampoule | Cancelled |
| 2696967 | Tambocor German | Inj 10 mg per ml, 15 ml ampoule | Cancelled |
| 2567121 | Flecainide Controlled Release Teva | Cap long-acting 200 mg | Cancelled |
| 2447363 | Tambocor | Inj 10 mg per ml, 15 ml ampoule | Cancelled |
| 2567695 | Flecainide BNM | Tab 50 mg | Cancelled |
One further cancelled authorization (2567113, Flecainide Controlled Release Teva, long-acting capsule 100 mg) is not shown. Approved indication text was not available for any of these products.
Safety Considerations
- Contraindications suggested by the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, potassium deficiency, myocardial infarction and coronary thrombosis, hemoglobinopathy, atrioventricular block, and sick sinus syndrome (including the familial form).
- Structural heart disease: flecainide is generally avoided in structural heart disease, including prior myocardial infarction, which limits its use in many patients with cerebrovascular disease.
- Proarrhythmia: a case report describes a Brugada pattern after flecainide overdose, and concerns about proarrhythmic effects in cardiovascular disease are discussed in the EAST-AFNET 4 analysis.
- Anticoagulant co-use: stroke and bleeding outcomes with combined DOAC and antiarrhythmic use have been studied (PMID 41152878), so co-prescribing needs attention.
- Pharmacology: flecainide has reported activity at Kv1.1, Kv1.2, Kv1.5, Kv1.7 and Kv3.1 potassium channels. These are pharmacology records, not clinical drug-drug interactions.
Please refer to the package insert for the full set of warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only Phase 3 trial targets post-PFO-closure arrhythmia, not stroke, and the literature mainly concerns atrial fibrillation management. The high TxGNN score probably reflects the known AF–stroke link. With no valid New Zealand authorization and significant cardiac contraindications, this is a research question rather than an actionable repurposing candidate.
To proceed, the following is needed:
- Results from NCT05213104, and ideally a trial with stroke or cerebrovascular events as the primary endpoint
- Mechanism of action data
- Package insert warnings and contraindications for a formal safety screen
- A defined patient population in whom flecainide is safe (without structural heart disease or conduction disease)
- Clarification of New Zealand availability, since all current authorizations are cancelled
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.