Impact of controlling atrial fibrillation on outcomes relevant to the patient: focus on dronedarone

Abstract

Atrial fibrillation (AF) is a substantial cause of mortality and morbidity in the Western world. It is a massive burden on health care systems, and its prevalence is expected to double over the next 20 years. Trials evaluating antiarrhythmic drugs or catheter ablation have focused on recurrence of arrhythmia, perhaps neglecting outcomes relevant to patients, such as symptoms, need for antiarrhythmic drugs, need for hospitalization, and rates of stroke and death. An association has been demonstrated between sinus rhythm and survival in several studies, and there is evidence emerging that successful catheter ablation may reduce rates of stroke and death. Similarly, dronedarone has been shown to reduce hospitalizations and death in patients with paroxysmal AF or persistent AF of recent onset, although it may cause adverse events in permanent AF. New antiarrhythmic drugs are a welcome addition to the armamentarium, since there are limitations to current antiarrhythmic drugs. In particular, sotalol, flecainide, and propafenone cannot be used safely in those with structural heart disease, and amiodarone has important adverse reactions that limit long-term use. Indeed, the use of conventional antiarrhythmic drugs may negate any survival benefit derived from maintaining sinus rhythm. Although dronedarone appears promising with respect to hard endpoints such as stroke and death in certain patients, it may not be safe for those with heart failure or those with permanent AF. Furthermore, the trials suggesting that dronedarone may impact on these endpoints were compared with placebo rather than with an active comparator group. Further "head-to-head" comparisons between dronedarone and other antiarrhythmic drugs are needed to determine whether this property is unique to dronedarone alone.

Keywords: ablation; antiarrhythmics; atrial fibrillation; dronedarone; rhythm; stroke.

Figure 1

Impact of dronedarone on the composite endpoint of cardiovascular hospitalizations or death in the ATHENA trial. Notes: *Standard therapy may have included rate control agents (beta-blockers, and/or Ca-antagonist and/or digoxin) and/or anti-thrombotic therapy (Vit. K antagonists and/or aspirin and other antiplatelets therapy) and/or other cardiovascular agents such as ACEIs/ARBs and statins. Reproduced with permission from The New England Journal of Medicine Adopted from Hohnloser SH et al.

Figure 2

ESC recommendations on choice of antiarrhythmic drug according to underlying pathology. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; HHD, hypertensive heart disease; CHD, coronary heart disease; HF, heart failure; LVH, left ventricular hypertrophy; NYHA, New York Heart Association. Adapted with permission from Camm A, Lip G, R DC, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. European Heart Journal. 2012;33:2719–47.

Figure 3

Agents for the prevention of recurrent AF after DC cardioversion. Note: **adapted from Lafuente-Lafuente et alCochrane Database Syst Rev. 2007 Oct 17;(4):CD005049. Abberviation: OR, odds ratio; CI, confidence interval.