According to Yuyun et al (2020), all major structural CVDs are linked to cardiac arrhythmias and as CVDs increase in sub-Saharan Africa, it is likely that the burden of arrhythmias is also rising. Furthermore, state the authors, arrhythmias are 'probably underdiagnosed' in sub-Saharan Africa.¹

Some of the reasons for this include the fact that the region faces significant challenges in managing CVDs due to insufficient health infrastructure, including limited arrhythmia services.¹

The region lacks specialist cardiac services, with many countries having fewer than five physicians per 10,000 people and 18% lacking a registered cardiologist.¹

High costs and limited health insurance systems further exacerbate the issue, making arrhythmia management unaffordable for most. Additionally, there is a severe shortage of epidemiological data on arrhythmias, hindering effective public health planning and resource allocation, they conclude.¹

A national registry study assessed treatment modalities for atrial fibrillation (AFib) in South Africa. Results showed that hypertension was the most common clinical characteristic (65.9%). Rhythm control, using class IC and III anti-arrhythmic drugs (AADs), was pursued in 36.1% of patients, while rate control, mainly with beta-blockers, was used for the rest.²

Warfarin was used by 75.2% for stroke prevention. AFib-related complications included heart failure (HF, 32.5%), stroke (8.3%), and transient ischaemic attack (5.3%).²

Therapeutic success was achieved in 86.8% of patients based on clinical judgment but only 70.2% met the electrocardiogram heart rate criterion of ≤80 bpm. The study highlighted a lack of strict rate control application, with results comparable to international data.²

What are the most common arrhythmias seen in clinical practice?

Arrhythmias are broadly categorised into bradyarrhythmias and tachyarrhythmias based on heart rate. They can also be classified according to their origin, transmission pathways, and associated syndromes.³

The clinical presentation of arrhythmias varies widely, ranging from asymptomatic cases to sudden cardiac arrest. Due to their paroxysmal nature, arrhythmias can be intermittent, making it difficult to accurately determine their prevalence.³

Tachyarrhythmia, defined by a ventricular heart rate of ≥100 beats per minute, is further classified by its origin into supraventricular tachycardia (SVT), and ventricular tachycardia (VT).³

SVT originates above the atrioventricular (AV) node and includes conditions such as AFib, atrial flutter, atrial tachycardia (AT), atrial premature complex, AV nodal re-entrant tachycardia, AV re-entrant tachycardia (AVRT), and AV junctional extrasystoles.³

VT, originating below the AV node, includes ventricular fibrillation (VFib), premature ventricular contractions (PVCs), and both sustained and non-sustained VT.³

AFib is the most common type of cardiac arrhythmia and is the leading cardiac cause of stroke. Risk factors for AFib include advanced age, high blood pressure, underlying heart and lung disease, congenital heart disease, and increased alcohol consumption.⁴

AADs still the mainstay of arrhythmia treatment

According to Kowey and Naccarelli (2024), 'misguided advice' about the role of AADs has led to a decline in the use of these agents in the treatment of arrhythmias. The authors stress that AADs have been, and will remain, the mainstay of chronic therapy of patients living with cardiac arrhythmias.⁵

In sub-Saharan Africa, AADs are available in most countries. Digoxin and amiodarone were available in all surveyed countries, followed by flecainide (80%), sotalol (75%), propafenone (22%), quinidine (17%), and mexiletine (4%).¹

Targeted ablative procedures for arrhythmias are a safe and effective option for patients with AFib unresponsive to medication and have seen rapid technological growth and increasing clinical interest in recent years. Reports highlight their effectiveness, quick procedural times, low risks, and fast recovery.⁶

Older drugs coming to the fore

Flecainide is a class IC AAD that was first synthesised in 1972. It was approved by the American Food and Drug Administration in 1984 for the suppression of sustained VT. Approval was based on the results of the Suppression of ventricular ectopic depolarisations by flecainide acetate, a new antiarrhythmic agent study, which showed significant suppression after one and two weeks of treatment (94.4% and 93.3%, respectively without significant adverse events (AEs).^7,8

In South Africa, flecainide is indicated for the treatment of sustained ventricular arrhythmias (VAs), AVNRT, Wolff-Parkinson-White Syndrome, and similar conditions involving accessory pathways with anterograde or retrograde conduction.⁹

It is also indicated for paroxysmal AFib in patients experiencing disabling symptoms, with a higher likelihood of success in arrhythmias of recent onset. Furthermore, flecainide is indicated for treating PVCs and non-sustained VT when these conditions cause disabling symptoms. Flecainide can also be used to maintain normal rhythm after cardioversion using other methods.⁹

Mechanism of action of flecainide

By slowing conduction, flecainide reduces the atrial wavelength, thereby impeding the maintenance of AFib. This effect is linked to its ability to decrease intracellular calcium accumulation by blocking sodium channels, which mitigates oxidative stress and atrial remodeling.⁴

Maintaining sinus rhythm

A Randomized Comparison of Amiodarone and Class IC Antiarrhythmic Drugs to Treat Atrial Fibrillation in Patients Paced for Sinus Node Disease: The Prevention Investigation and Treatment: A Group for Observation And Research On Atrial Arrhythmias (PITAGORA) Trial as well as the FLEC-SL trials underscore its effectiveness in maintaining sinus rhythm, with flecainide proving non-inferior to amiodarone in some cases.^10,11,12

The PITAGORA study assessed whether class IC AADs like flecainide and propafenone were noninferior to amiodarone in patients with sinus node disease. Patients were randomised in a 1:1 ratio to receive either amiodarone or class IC AADs.¹⁰

Over an average follow-up of 20-months, the primary endpoint (mortality, permanent AT, CV hospitalisation, atrial cardioversion, or AAD change) occurred in 30.7% of patients on class IC AADs and 40% of those on amiodarone.¹¹

One-year freedom from AT episodes lasting >10 minutes, one day, and seven days was 40%, 73%, and 91% for amiodarone and 28%, 78%, and 86% for class IC AADs.¹¹

More recently, Rillig et al (2024) evaluated the safety and efficacy of rhythm control therapy with flecainide and propafenone in patients with early recurrence of AFib as part of the The Early Treatment of Atrial Fibrillation for Stroke Prevention Trial.¹²

The study included 1395 participants and focused on two primary outcomes: Safety, defined as death, stroke, or serious AEs, and efficacy, defined as CV death, stroke, and hospitalisation for worsening heart failure or acute coronary syndrome.¹²

The analysis revealed that the primary efficacy outcome occurred less frequently in patients treated with flecainide or propafenone (3/100 patient-years) compared to those who did not receive flecainide or propafenone (4.9/100 patient-years).¹²

Additionally, the primary safety outcomes were lower in the flecainide and propafenone group (2.9/100 patient-years) compared to the non-AAD group (4.2/100 patient-years). The rate of maintaining sinus rhythm at two years was comparable between the AAD group (88%) and the non-AAD group (82%).¹²

Ventricular tachycardia

In terms of VT, flecainide’s role is complex. The Cardiac Arrhythmia Suppression Trial (CAST) revealed that flecainide, when used for asymptomatic VAs post-myocardial infarction, increased the risk of arrhythmia-related and all-cause mortality, leading to its premature discontinuation in some patients. However, Kowey and Naccarelli point out that in the post-CAST era, data suggest that flecainide may be used in patients with minimal coronary artery disease.^5,10

Acute setting

In acute settings, flecainide’s efficacy has also been shown. Both oral and intravenous (IV) forms of the flecainide have proven effective in converting recent-onset AFib to sinus rhythm. Notably, oral flecainide administered as a single loading dose (so-called 'pill-in-the-pocket') has been shown to be more effective than IV amiodarone within eight hours.⁷

Conclusion

CVDs are a leading cause of death in sub-Saharan Africa, with a rising prevalence of cardiac arrhythmias linked to the increasing CVD burden. AADs, particularly flecainide, are essential for treating these conditions. In arrhythmia patients with minimal or no structural heart disease, studies demonstrate flecainide’s efficacy and safety. Addressing healthcare gaps and improving access to AADs could significantly enhance arrhythmia management in sub-Saharan Africa.

References

1. Yuyun MF, Bonny A, Ng GA, et al. A Systematic Review of the Spectrum of Cardiac Arrhythmias in Sub-Saharan Africa. Glob Heart. 2020
2. Jardine RM, Fine J, Obel IW. A survey on the treatment of atrial fibrillation in South Africa. S Afr Med J, 2014. 
3. Desai DS, Hajouli S. Arrhythmias. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558923/
4. Nesheiwat Z, Goyal A, Jagtap M. Atrial Fibrillation. [Updated 2023 Apr 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526072/
5. Kowey PR, Naccarelli GV. Antiarrhythmic Drug Therapy: Where Do We Go from Here? Circulation, 2024.
6. McBride S, Avazzadeh S, Wheatley AM, et al. Ablation Modalities for Therapeutic Intervention in Arrhythmia-Related Cardiovascular Disease: Focus on Electroporation. J Clin Med, 2021.
7. Andrikopoulos GK, Pastromas S, Tzeis S. Flecainide: Current status and perspectives in arrhythmia management. World J Cardiol, 2015.
8. Hodges M, Haugland JM, Granrud G, et al. Suppression of ventricular ectopic depolarizations by flecainide acetate, a new antiarrhythmic agent. Circulation, 1982.
9. Professional Information. Tambacor. 2012. [Internet]. Available at: https://www.sahpra.org.za/wp-content/uploads/2020/04/Tambocor_PI_iNova-Pharmaceuticals_MCC-Format-20-April-2012.pdf
10. Kirchhof P, Andresen D, Bosch R, et al. Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial. The Lancet, 2012.
11. Gulizia M, Mangiameli S, Orazi S, et al. PITAGORA Study Investigators. A randomized comparison of amiodarone and class IC antiarrhythmic drugs to treat atrial fibrillation in patients paced for sinus node disease: the Prevention Investigation and Treatment: A Group for Observation and Research on Atrial arrhythmias (PITAGORA) trial. Am Heart J, 2008.
12. Rillig A, Eckardt L, Borof K, et al. Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial. EP Europace, 2024.