RYTHMOL

Key points

Favourable opinion for maintenance of reimbursement only in the prevention of recurrences of documented supraventricular tachycardias when the need for treatment has been established and in the absence of impairment of left ventricular function.

Clinical benefit now :

• Moderate (previously it was substantial) in the prevention of recurrences of documented supraventricular tachycardias when the need for treatment has been established and in the absence of impairment of left ventricular function ;
• Insufficient to justify its public funding cover (previously it was substantial) in the treatment and prevention of recurrences of ventricular rhythm disorders, and in the prevention of electric cardiac shocks in certain patients with an implantable cardioverter defibrillator (ICD).

Role in the care pathway ?

Supraventricular tachycardias

- Prevention of recurrences of atrial fibrillation

Antiarrhythmic treatment may be considered as long-term therapy to maintain sinus rhythm in the event of symptomatic recurrent paroxysmal or persistent AF. It is not generally initiated from the first episode of AF. Long-term antiarrhythmic treatment is aimed at improving symptoms and preventing recurrences of symptomatic AF. It falls within the scope of specialised management with a cardiological opinion and at least annual ECG monitoring. Catheter ablation may be a first-line therapeutic alternative in specific situations or a second-line alternative in the event of failure of medicinal treatment. It requires oral anticoagulant therapy and is reserved for cardiac rhythm specialists.

Role of the medicinal product in the care pathway :

In patients with paroxysmal or persistent atrial fibrillation, in combination with lifestyle and dietary measures and control of risk factors, propafenone (class IC antiarrhythmic drug) is a therapeutic alternative for the maintenance of sinus rhythm only in patients without underlying structural heart disease (ischaemic heart disease or impairment of left ventricular function), taking into account new clinical efficacy data suggesting a moderate effect size on the prevention of recurrences of atrial fibrillation compared to the control group (placebo or the absence of treatment) in view of its safety profile marked by frequent adverse effects (in particular pro-arrhythmic), and uncertainties with respect to a potential risk of excess mortality with class IC antiarrhythmic drugs in atrial fibrillation due to limited data.

Due to the excess mortality observed compared to placebo with flecainide (another class IC antiarrhythmic drug) in off-label indications [patients with a history of myocardial infarction with a reduced left ventricular ejection fraction and ventricular hyperexcitability (CAST trial)], and the resulting uncertainties in the indications of the MA, with a potential risk of excess mortality that cannot be eliminated, the Committee recommends the use of class IC antiarrhythmic drugs for a short period and in strict compliance with the MA conditions, particularly with respect to their contraindications (heart failure, history of myocardial infarction, conduction disorders, etc.). It also recommends that the benefits of maintaining treatment for more than a month following cardioversion be systematically reassessed and encourages a prescription duration that is as short as possible.

In patients with permanent atrial fibrillation, the Committee reiterates that oral antiarrhythmic drugs no longer have a role in the prevention of recurrences.

- Prevention of recurrences of other supraventricular tachycardias

The therapeutic strategy for the prevention of recurrences of supraventricular rhythm disorders apart from atrial fibrillation (focal atrial tachycardias, common atrial flutter, atrioventricular nodal re-entry tachycardia (AVNRT), atrioventricular re-entry tachycardia (AVRT)) is based on catheter ablation as a first-line approach. Medicinal treatment with beta-blockers or non bradycardia-inducing calcium channel blockers is recommended pending or following refusal or failure of ablation. The use of oral antiarrhythmic drugs has become marginal.

Role of the medicinal product in the care pathway :

Propafenone remains recommended in focal atrial tachycardias and atrioventricular re-entry tachycardia (AVRT), in the absence of structural or ischaemic heart disease in combination with lifestyle and dietary measures and control of risk factors.

The Committee considers that all the oral antiarrhythmic drugs concerned by the reevaluation no longer have a role in other types of supraventricular arrhythmia, including, in particular, nodal tachycardias or Bouveret-Hoffmann syndrome.

Ventricular rhythm disorders

- Treatment of recurrences of ventricular rhythm disorders

These are primarily frequent ventricular extrasystoles or symptomatic, non-sustained ventricular tachycardias in patients with left ventricular dysfunction or certain forms of arrhythmogenic cardiomyopathy.

The 2016 European guidelines indicate beta-blockers as the first-line treatment. In the event of intolerance or failure to respond to this class, oral amiodarone (off-label) with the usual precautions for use as regards its safety may be considered. Class IA and IC antiarrhythmic drugs are not recommended.

The ablation of arrhythmogenic foci is envisaged as an adjuvant treatment for ventricular tachycardias with underlying heart disease, in addition to the other treatments.

Role of the medicinal product in the care pathway :

In the treatment of disabling, symptomatic documented ventricular rhythm disorders, the proprietary medicinal product RYTHMOL (propafenone) no longer has a role in the care pathway.

- Prevention of recurrences of ventricular rhythm disorders

With the exception of certain specific cardiac diseases, the prevention of recurrences of ventricular arrhythmias is based on an implantable cardioverter defibrillator and, more rarely, on antiarrhythmic drugs. The decision to implant an ICD requires the opinion of a cardiac rhythm specialist. Implantation is only considered in authorised centres in patients in whom the reasonable expectancy of survival with a satisfactory functional status is more than 1 to 2 years and in patients over 30 years of age.

Beta-blockers (excluding sotalol) are recommended as first-line treatment in patients with ventricular arrhythmia.

In the event of failure of or contraindication to beta-blockers, the European guidelines indicate antiarrhythmics. Antiarrhythmic drugs are used as an adjuvant therapy in the treatment of patients with ventricular arrhythmias. The choice of antiarrhythmic drug must take into account the causal disease and/or the associated heart condition.

Furthermore, interventional procedures are alternatives :

• The ablation of arrhythmogenic foci is considered as a second-line treatment of recurrent idiopathic ventricular tachycardias, following the failure of pharmacotherapy.
• Ablation is generally performed percutaneously (percutaneous catheter ablation), by the subepicardial route in rare cases and, in exceptional cases, surgically.
• Finally, other invasive or surgical treatments, such as myocardial revascularisation, ventricular aneurysm resection, sympathetic denervation, short-term mechanical circulatory support, heart transplant, the use of a total artificial heart device or anaesthetic sedation, represent special situations, with implementation decided upon on a case-by-case basis following a specialised opinion.

Role of the medicinal product in the care pathway :

In the prevention of disabling, symptomatic documented ventricular rhythm disorders, the proprietary medicinal product RYTHMOL (propafenone) no longer has a role in the care pathway.

Prevention of cardiac shocks in patients with an implantable cardioverter defibrillator (ICD)

The prevention of unnecessary electric shocks and electrical storms is a major objective of treatment in patients with an ICD. Beta-blockers are recommended as first-line treatment in order to reduce appropriate and inappropriate ICD shocks.

Antiarrhythmic drugs are mentioned in the European guidelines to minimise both appropriate and inappropriate ICD interventions in patients fitted with an ICD, in particular oral amiodarone as second-line pharmacotherapy, in combination with a beta-blocker (off-label use) particularly in the presence of coronary insufficiency and/or impaired left ventricular function.

Role of the medicinal product in the care pathway :

In the prevention of cardiac shocks, the proprietary medicinal product RYTHMOL (propafenone) no longer has a role in the care pathway.

Special recommendations

The Committee maintains its recommendation of reserving initial prescription to cardiologists, given :

• the need for pre-treatment screening with assessment of heart function, in particular involving the performance of an ECG and, if necessary, additional cardiac imaging, the need to evaluate the benefit of prescription, taking into account the clinical indication, the aetiology, the patient’s comorbidities and, in particular, in view of :

• the specific safety profile of oral antiarrhythmic drugs (pro-arrhythmic effects for all drugs and extracardiac effects for amiodarone),
• the updated efficacy profile and the Committee’s new guidelines concerning the role of each drug in the care pathway.

The Committee reiterates that if it is necessary to change treatment, any overlapping of prescriptions of antiarrhythmic drugs should be avoided, since this could exacerbate their toxicity.