Long-term antiarrhythmic drug treatment after atrial fibrillation ablation: does a too obstinate rhythm control strategy bring serious risk of proarrhythmia to ablated patients?

Rather erratic changes have characterized pharmacological protocols for treatment or secondary prophylaxis of atrial fibrillation (AF) after the advent of transcatheter ablation techniques.1 Indeed, starting from the end of the first decade of the 2000s, conflicting therapeutic orientations emerged. Importantly, several protocols were issued aiming to exclude Class I and III antiarrhythmics agents (Vaughan Williams Classification) from programmes of routine prophylaxis of AF recurrences in ablated patients.2 In reality, the choice to discourage the chronic use of these drugs has even recently been confirmed because they have the potential to cause serious damage to the ablated patients through the full range of iatrogenic proarrhythmia events in exchange for the unacceptable compensation of a better protection against AF relapses.3 In contrast, in patients deemed not eligible for ablation, two possible operative behaviours were suggested: on the one hand, targeted strategies were implemented for rhythm retrieval (either pharmacological conversion to sinus rhythm or external electrical cardioversion) as well as rhythm control even by means of Class I and III antiarrhythmics; on the other hand, in patients deemed likely not to achieve stable sinus rhythm, a scrupulous anticoagulation was recommended, while the mean ventricular response had to be kept between 60 b.p.m. and 90 b.p.m. with the use of agents depressant of atrioventricular (AV) nodal conduction when necessary, a so-called rate control strategy. However, some alternative operational messages appear to be emerging in recent times. A first message that has caused true upheaval of the established medical conduct regarding AF has come from the Castle-AF study.4 Based on this study, ablation for AF in patients with heart failure would be associated with a significantly lower rate of a composite of death from any cause and hospitalization for worsening heart failure than was medical therapy. A second message, not in keeping with the invitation to ablate contained in the Castle-AF study, has arisen from preliminary findings coming from the CABANA trial (sponsored by the US National Institutes of Health).5,6 Indeed, based on the analysis of the preliminary results of CABANA, conducted according to the intention-to-treat principle, and reported as Supplementary material online accompanying the present letter, ablation would not generate significant benefits over a 5 years of follow-up compared with antiarrhythmic drug therapy (ADT) with regard to the composite of death, disabling stroke, severe bleeding, and cardiac arrest, as well as for each of the four components taken individually. In addition, as a third message, Arbelo et al. reporting a European survey of AF ablation that included 1300 patients from 72 European institutions found that among a patient population of which more than two-thirds had paroxysmal AF, 65% of patients were discharged post-ablation on an antiarrhythmic medication; furthermore, more importantly, 49% and 40% remained on antiarrhythmic medication at 12 months and after 12 months post-ablation, respectively.7 In summary, in ablated patients, the usual administration of Class IC drugs, namely flecainide or propafenone, or Class III, preferably sotalol, in order to avoid possible AF recurrences, as well as the customary chronic anticoagulation, mostly warfarin, in order to prevent the cardio-embolic risk, has emerged as a resounding denial of the original axiom according to which ablation would gain the advantage of exempting those patients from pharmacological therapies known for their pro-arrhythmic or pro-haemorrhagic potential. In reality, today, the model implemented in the majority of dedicated centres consists of ablation followed by the administration of antiarrhythmics and warfarin, not only in the peri- and post-procedural stages (blanking period), but indefinitely over time.8 All of this is leading to a revival of drugs such as flecainide, propafenone, or sotalol, which had previously been accused of being harmful because of a dangerous risk of paradoxical pro-arrhythmia. Nevertheless, the surveys available in the literature have documented that the desire to be free of symptoms largely outweighs the desire to stop ADT. In the ESC-EHRA AF ablation long-term registry, the reason for ablation of paroxysmal AF was symptoms in 93% of the procedures, whereas only 30.6% of procedures were performed out of a desire for a drug-free lifestyle.7 In the meantime, it is possible that the ability to manage ADT has been improved. For example, if not already the case, beta-blocking agents are usually added to Class IC drugs.9 This measure is useful for minimizing the risk described in the literature10 of rapid atrial flutter with a 1:1 conduction ratio, imputed to 1C drugs for their intrinsic vagolytic effect at the AV node level. In conclusion, the modified modalities of AF prophylaxis in ablated patients are leading to a massive and prolonged use of 1C drugs and sotalol for the sole purpose of obtaining a longer lasting therapeutic performance of the ablation procedures. Based on the known dangerous clinical correlates of these drugs (IC and sotalol), in many cases, common sense considerations and caution should prompt the physician to make a switch towards a rate control strategy, since the risk of proarrhythmia is almost null with the use of beta-blockers or verapamil—to be used for the pharmacological modulation at the level of AV nodal conduction—while it is always incumbent for IC drugs and even for sotalol. A debate on this point would then be more than ever appropriate and useful. Conflict of interest: none declared.