Oral loading of propafenone: restoring its role before restoring rhythm—authors’ reply

We wish to thank Martignani et al.1 for their critical Letter to the Editor according to our article recently published in Europace2 where they question our proposal that propafenone should not be generally excluded from cardioversion of paroxysmal atrial fibrillation in patients with structural heart disease. Recent 2016European Society of CardiologyGuidelines for the Management of Atrial Fibrillation3 support the use of propafenone for acute pharmacological cardioversion in patients with new onset of atrial fibrillation. However, their restriction that propafenone should only be given to patients without structural heart disease3 particularly bases on CAST (the Cardiac Arrhythmias Suppression Trial),4 where long-term administration of flecainide and encainide, two other Class Ic antiarrhythmic agents without β-blocking effects, increased mortality when given to patients with ventricular arrhythmias and coronary artery disease. Our data and conclusions2 only refer to the administration of single oral doses of propafenone for cardioversion of paroxysmal atrial fibrillation. Therefore, the fact that the pharmacokinetics of propafenone may be different in different oxidisers5 only plays a minor role since we do not recommend long-term treatment. There is no doubt that administration of Class Ic antiarrhythmic drugs in patients with atrial fibrillation may switch to atrial flutter and that, therefore, concomitant treatment with a β-blocker or a non-dihydropyridine calcium channel blocker is recommended.3 Therefore, it might be essential that single oral doses of 600 mg propafenone possess β-blocking effects by themselves.2 We fully agree that β-blockers show several side effects and contraindications such as asthma bronchiale, severe obstructive lung disease, systolic heart failure, hypotension, atrio-ventricular-blocks, and sick sinus syndrome.1 Therefore, even single oral doses of propafenone should be given carefully to patients with these diseases. On the other hand, we believe that our findings that oral administration of 600 mg propafenone shows clinically effective beta-blockade2 clearly distinguish propafenone from other Class Ic antiarrhythmic drugs in cardioversion of paroxysmal atrial fibrillation since β-blockers are even indicated in patients with coronary artery disease, and the fact that the use of propafenone for pharmacological cardioversion is restricted to patients without structural heart disease3 particularly bases on the results of the CAST4 where it was shown that (i) only long-term treatment (ii) with other Class Ic antiarrhythmic drugs may increase mortality when given to patients with ventricular arrhythmias and coronary artery disease. However, to our knowledge, similar negative effects never were shown with single oral doses of propafenone. In addition, we believe that our results2 harmonize with recent guidelines3 that propafenone should be given to patients with (paroxysmal) atrial fibrillation first of all in hospital with strict electrocardiogram monitoring for at least 8 h and only to patients without known side effects or contraindications of β-blockers. However, particularly coronary artery disease should not be seen as a contraindication against single oral doses of propafenone, i.e. a drug showing clinically effective β-blockade. Finally, we fully agree with Martignani et al.1 that a clinical outcome trial on administration of single oral doses of 600 mg propafenone in patients with paroxysmal atrial fibrillation is warranted to investigate its potential side effects in patients with structural heart disease.