TAKE-HOME POINTS
■ Dronedarone increased the risk for hospitalization and death from heart failure during clinical study, but it may lack several serious adverse reactions linked to amiodarone.
■ Dronedarone is generally better tolerated than amiodarone.
■ Amiodarone is more effective than dronedarone at maintaining normal sinus rhythm in patients with AF.
■ The retail cost of amiodarone is significantly less than that of dronedarone.
■ Oral dosing is typically twice daily for both drugs, but amiodarone requires more extensive monitoring for safety.
Dronedarone (Multaq), approved by the FDA in 2009, is the latest antiarrhythmic drug to enter the US market. Dronedarone is a derivative of amiodarone, which was modified in an attempt to reduce its serious toxicities. Dronedarone has the therapeutic effects of all four classes of antiarrhythmic agents as defined by Vaughn-Williams criteria, including the blockade of sodium channels, beta-adrenergic receptors, potassium channels, and calcium channels.1 Dronedarone can reduce the risk of cardiovascular hospitalization in select patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter.2 The quest to develop an antiarrhythmic drug that is both highly effective and well-tolerated remains an ongoing challenge.
Neither rate control nor rhythm control, the two most common treatments for AF, has been determined to be superior based on the primary end points of trials, nor have trial data demonstrated a statistical difference in all-cause mortality.3-8 Based on this evidence and its superior tolerability, rate control is generally the initial treatment of choice for patients with atrial fibrillation. Rhythm control is initiated in patients who remain symptomatic despite consistent rate control.9 Antithrombotic or anticoagulant therapy is incorporated with both strategies.
While the chemical structures of dronedarone and amiodarone (Cordarone, Pacerone) are similar, they have significant therapeutic differences.10 Both agents have drug interactions via cytochrome P-450 enzymes, which include beta-adrenergic blockers, calcium channel blockers, cholesterol medications (eg, statins), digoxin, and grapefruit juice.10 Concomitant use of drugs or dietary supplements that prolong the QT interval is contraindicated with both agents because of an increased risk of torsades de pointes.1,10,11 Dronedarone can safely be used with warfarin, but warfarin doses should be reduced when used with amiodarone; regular monitoring of prothrombin time and international normalized ratio should also occur.11Table: Key differences between amiodarone and dronedarone in the online version of this article explains further differences.
SAFETY
Amiodarone has a relatively lower potential for proarrhythmia and does not negatively impact mortality in patients with structural heart disease.12 However, it may cause skin discoloration (4-9%), optic neuropathy or neuritis (1-2%), thyroid dysfunction (1-6%), pulmonary toxicity (1-7%), elevated liver enzymes (15-30%), and hepatitis or cirrhosis (less than 3%).12 The most frequently reported adverse reactions with dronedarone include GI problems (2-9%, number needed to harm [NNH] 28), asthenia (7%, NNH 50), bradycardia (3%, NNH 43), and common skin reactions (5%, NNH 70).13 Increases in serum creatinine (51%, NNH 30) and QTc prolongation (average recurrence interval 1.1%, NNH 91) may also occur.2
In a short-term trial of patients with persistent AF, fewer patients prematurely discontinued dronedarone than amiodarone (10.4 versus 13.3%, P = .227).14 The major safety end point was defined as the first occurrence of thyroid, hepatic, pulmonary, neurologic, skin, eye, or GI-specific events or premature drug discontinuation following an adverse event. At 12 months, the incidence of the major safety end point was 39.3% for dronedarone and 44.5% for amiodarone (P = .129). The incidence of treatment-related adverse events and heart failure was similar among the groups (12% and 6.4% for dronedarone and 11% and 7.5% for amiodarone, respectively). Dronedarone users had a significantly lower risk of hemorrhagic events than amiodarone users (P = .03).