A 68-year-old man presented to the emergency department for a sudden onset of palpitation, fatigue, and dyspnea on exertion. FC was the medical doctor on duty. The patient denied chest pain and reported a long-standing history of hypertension, but there was no history of coronary artery disease and no other cardiovascular risk factors. Home medications were bisoprolol (5 mg daily) and enalapril (20 mg daily).
Twelve lead-ECG showed atrial fibrillation (AF) with a ventricular rate of 160 bpm; blood tests were unremarkable. The patient was treated with intravenous propafenone with successful cardioversion to sinus rhythm. Considering the risk factors for cardioembolic stroke (hypertension and age determining a CHA2D2-VASC score of 2 points),1
oral anticoagulant therapy was started.
Over the previous months the patient had had two emergency department visits for palpitation and dyspnea on exertion due to AF with high ventricular rate; in both cases he had spontaneous cardioversion to sinus rhythm in the emergency department. After the first episode of AF, a transthoracic echocardiogram was performed that showed moderate increased left ventricular wall thickness (16 mm), normal left ventricular and atrial sizes, and normal systolic function. Thyroid function tests were normal.
Considering the disabling symptoms during the recurrences of AF and the inability to attain adequate rate control, FC decided to adopt a rhythm control strategy for the maintenance of sinus rhythm. Which antiarrhythmic treatment should be started in a patient with AF and left ventricular hypertrophy without coronary artery disease?
In order to choose the appropriate therapy, FC decided to look at two of the most authoritative clinical guidelines on the topic, edited respectively by the American College of Cardiology Foundation/American Heart Association (ACCF/AHA)2
and by the European Society of Cardiology (ESC).4
As the recommendations were discordant, FC was puzzled. In fact, while ACCF/AHA suggested amiodarone as first-line treatment in this clinical setting, ESC guidelines recommended dronedarone ().
Table 1 Choice of antiarrhythmic drug according to underlying pathology: comparison of ACCF/AHA2,3 and ESC4 guidelines
So, FC wondered: “Was dronedarone actually useful to maintain sinus rhythm? Compared to amiodarone, was dronedarone more efficacious and safe? What was the available evidence? Did any study evaluate clinical relevant end points such as mortality?”
AF is the most common sustained arrhythmia. It occurs in 1%–2% of the general population and its prevalence increases with age.5
It may cause disabling symptoms, with impairment of both functional status and quality of life.
guidelines distinguish four types of AF: (1) “first detected or diagnosed”, (2) paroxysmal, (3) persistent, and (4) permanent AF. “First detected or diagnosed AF” is AF identified for the first time, independently of its duration or the presence of symptoms. Paroxysmal AF is defined as recurrent AF that terminates spontaneously in less than 7 days, usually in less than 48 hours. Persistent AF is AF lasting longer than 7 days or requiring pharmacological or electrical cardioversion to sinus rhythm. Finally, permanent AF lasts more than 1 year. Moreover, into the category of persistent AF, ESC distinguishes a “long-standing persistent AF” with 1 year or more of duration after the adoption of a rhythm-control strategy. For permanent AF, on the contrary, rhythm-control strategy is not pursued.
AF is associated with increased morbidity and mortality, mainly due to stroke and heart failure.7
Management of AF patients is focused on reducing symptoms and preventing the complications associated with arrhythmia. Two therapeutic strategies can be identified: a “rhythm-control” option, when antiarrhythmic drugs, with or without electrical cardioversion, are used to restore sinus rhythm, and a “rate-control” strategy, the main objective of which is to control ventricular response rate. In addition, stroke prophylaxis therapy is required in most AF patients and antithrombotic therapy is prescribed according to stroke risk stratification schemes, such as CHA2D2-VASC,1
taking into account also the patient’s risk of bleeding.
To date, randomized controlled trials have failed to demonstrate the superiority of one strategy over the other.9
Many drugs have been employed as antiarrhythmic options: amiodarone seems to be the most effective in preventing recurrences of AF,12
but its use is limited by toxicity.14
Dronedarone, a noniodinated benzofuran similar to amiodarone, was developed as an antiarrhythmic agent for patients with AF. Because of the structural differences between amiodarone and dronedarone, particularly the deletion of iodine molecules, dronedarone has been supposed to have similar efficacy to amiodarone but fewer thyroid and pulmonary side effects.
This systematic review looked at the randomized controlled trials (RCTs) conducted to date that compared treatment with dronedarone versus placebo or amiodarone in patients with AF. Our aim was to assess the efficacy and side-effects of dronedarone and to critically evaluate current evidence.