A structured framework for anti-arrhythmic therapy
The 2025 European Heart Rhythm Association (EHRA) Practical Compendium of AADs formalises this integrated approach by categorising therapy into appropriate, backup, and complementary use. This framework is intended to align drug therapy more clearly with procedural strategies such as ablation and device-based interventions, while also acknowledging real-world variability in access and patient suitability.¹

Within this structure, appropriate therapy refers to situations in which AADs serve as primary long-term management, backup therapy describes use when ablation or devices are unavailable or unsuitable, and complementary therapy reflects their role alongside procedures, including peri-ablation support and rhythm stabilisation.¹

Dr Merino emphasises that this reflects clinical reality rather than theoretical classification, particularly given the frequent use of AADs before and after ablation procedures and their role in reducing early post-ablation arrhythmia recurrence.²

South African practice and the role of flecainide
In South Africa, these global frameworks intersect with significant resource constraints that influence treatment sequencing. Prof Ashley Chin, Associate Professor of Cardiology and Electrophysiology at Groote Schuur Hospital and the University of Cape Town’s Private Academic Hospital, explains that flecainide commonly occupies the appropriate category in local practice because access to catheter ablation is often delayed or limited by long waiting lists in the state sector.

In this context, flecainide is widely used as a rhythm-control agent in patients with paroxysmal AFib and no structural heart disease. Prof Chin describes it as an effective option for maintaining sinus rhythm, particularly when ablation is not immediately available or when patients have not yet failed pharmacological therapy.

He notes that in the public sector, ablation is typically reserved for patients who fail or cannot tolerate anti-arrhythmic medication, making drug therapy the practical first-line strategy in many cases.

Evolving classification of anti-arrhythmic drugs
The traditional Vaughan Williams framework has been expanded in recent years through mechanistic refinements, including the Oxford 2018 revision. This modern interpretation recognises additional pharmacological subclasses reflecting a shift in thinking from 'what channel does the drug block' to what mechanism is driving the arrhythmia'.¹

Prof Merino highlights that anti-arrhythmic pharmacology is often incorrectly viewed as static, despite ongoing advances in ion channel targeting, autonomic modulation, and drug repurposing. According to Merino et al, these developments and the updated classification system introduce newer conceptual categories, including sinus node modulators and agents targeting the late sodium current, reflecting an evolving understanding of arrhythmia pharmacotherapy.²

Flecainide in clinical decision-making
Flecainide remains a Class Ic anti-arrhythmic agent primarily used for rhythm control in supraventricular arrhythmias, particularly AFib, atrial flutter-related rhythms, and re-entrant tachycardias. It is effective for pharmacological cardioversion, maintenance of sinus rhythm, and selected cases of episodic self-termination using a ‘pill-in-the-pocket’ strategy in carefully screened patients.¹

Its role is most clearly defined in patients with paroxysmal AFib and structurally normal hearts. Prof Chin emphasises that patient selection is central to safe use, noting that flecainide is appropriate for individuals without structural heart disease or coronary artery disease. In patients who experience frequent AFib episodes, he describes flecainide combined with a β-blocker as an effective rhythm-control strategy, with catheter ablation reserved as a second-line option when pharmacological therapy is insufficient.

Amiodarone, by contrast, is generally reserved for patients with underlying structural heart disease and is not considered suitable for long-term rhythm control due to its cumulative toxicity profile. This distinction is particularly important in chronic management decisions where long-term safety becomes a dominant consideration.

Flecainide is contraindicated in ischaemic heart disease and structural myocardial abnormalities due to increased risk of pro-arrhythmia and mortality.¹ This is especially relevant in South Africa, where rheumatic heart disease and cardiomyopathy remain prevalent contributors to structural cardiac disease. Prof Chin therefore emphasises that flecainide should be avoided in patients with rheumatic heart disease, with rate-control strategies often preferred in such cases.

He also cautions against extending emerging evidence supporting broader flecainide use into structurally abnormal hearts without specialist oversight, highlighting the need for electrophysiology or cardiology-level interpretation in these scenarios.

Practical limitations of pill-in-the-pocket strategies
Although pill-in-the-pocket flecainide is supported in selected international guidelines, its implementation in South African public-sector practice is limited. Prof Chin explains that resource constraints, delayed presentation, and limited capacity for supervised initiation often prevent formal inpatient testing of this strategy. As a result, it is seldom used in routine state practice despite its theoretical utility in low-risk patients.

Monitoring and safety considerations
Safe use of flecainide requires structured electrocardiogram (ECG) monitoring, with particular attention to QRS duration and conduction changes. Even in resource-limited settings, baseline and follow-up ECG assessment remains essential. Prof Chin notes that ECG access is generally available even in rural environments, making this a feasible minimum monitoring requirement.

Clinically significant warning signs include QRS prolongation >50% of baseline, as well as the emergence of symptoms such as palpitations, dizziness, or syncope. While early reassessment within four to five days of initiation is ideal, this is not always practical in systems with limited outpatient capacity. Nevertheless, lower-dose regimens are often well tolerated even when ideal monitoring intervals cannot be strictly achieved.

Long-term safety profile and clinical positioning
Flecainide’s relatively favourable long-term safety profile compared with amiodarone supports its role as a medium-term rhythm-control option in appropriately selected patients. Prof Chin emphasises that while it is not typically intended as lifelong therapy, it provides a safer intermediate strategy in patients requiring sustained rhythm control without structural heart disease.