From the Guidelines
Multaq (dronedarone) 400mg twice daily is not recommended as a first-line treatment for atrial fibrillation due to its significant safety concerns and risk profile, as highlighted in the 2022 European Heart Journal review by the European Society of Cardiology working group on cardiovascular pharmacotherapy 1. The medication carries a higher risk of proarrhythmia in patients with structural heart disease and should be avoided in patients with permanent atrial fibrillation, severe heart failure, liver or lung toxicity, and should not be used with strong CYP3A inhibitors or QT-prolonging drugs. Some of the main adverse effects of antiarrhythmic drugs, including Multaq, are:
- Increased risk of bradycardia and AVB
- Intracardiac conduction block
- Heart failure in patients with poor left ventricular function
- Hypotension
- Anticholinergic effects, such as dry mouth, constipation, and urinary retention
- Cognitive impairment
- Fatal hepatotoxicity According to the 2016 ESC guidelines for the management of atrial fibrillation 1, rate control strategies with beta-blockers or calcium channel blockers, combined with anticoagulation for stroke prevention, offer safer long-term management for most patients with atrial fibrillation. Key points to consider when managing atrial fibrillation include:
- Monitoring the ECG and serum K+ and Mg2+ levels
- Avoiding the use of QT-prolonging drugs
- Individualizing doses according to the QTc interval, renal function, and serum K+ and Mg2+ levels
- Regular monitoring of liver enzymes, especially during the first six months of treatment
- ECG monitoring to assess QT interval Overall, the safety profile of Multaq is less favorable than other antiarrhythmic options, and its use should be carefully considered on a case-by-case basis, taking into account the individual patient's risk factors and medical history.
From the FDA Drug Label
WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION In patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure; MULTAQ doubles the risk of death. In patients with permanent atrial fibrillation, MULTAQ doubles the risk of death, stroke and hospitalization for heart failure. MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure. MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm.
The safety of Multaq 400mg BID for atrial fibrillation is a concern due to the increased risk of:
- Death
- Stroke
- Heart failure in patients with decompensated heart failure or permanent atrial fibrillation. Multaq is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure, and in patients in atrial fibrillation who will not or cannot be cardioverted into normal sinus rhythm 2.
From the Research
Safety of Multaq 400mg BID for Atrial Fibrillation
- The FDA has approved dronedarone (Multaq) for oral treatment of atrial fibrillation and flutter 3.
- Dronedarone is chemically similar to amiodarone but has a different pattern of short-term adverse effects, including more gastrointestinal disorders but less frequent thyroid disorders, neurological disorders, hypersensitivity reactions, hypertension, and QT prolongation 4.
- Common adverse effects of dronedarone include diarrhoea, nausea and vomiting, and cutaneous disorders, as well as transient elevation of creatinine levels and cases of renal failure 4.
- Dronedarone has been associated with a statistically significant increase in mortality in a trial in 627 symptomatic patients free of arrhythmias, but no statistically significant difference in mortality was found in a trial including 4630 patients with atrial fibrillation and a lower risk of cardiovascular events 4.
- A study found that dronedarone had lower mortality rates compared to other AF patients, with a hazard ratio of 0.41, and lower mortality rates than expected from the general population 5.
- The risk of liver disease was not increased with dronedarone use, with a hazard ratio of 0.57 5.
- Dronedarone is less effective than amiodarone in maintaining normal sinus rhythm, but has a better tolerability profile 4, 6, 7.
- Dronedarone is currently recommended in patients with paroxysmal and persistent AF to achieve rate and rhythm control, excluding cases of severe or unstable congestive heart failure 7.
Efficacy of Multaq 400mg BID for Atrial Fibrillation
- Dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation 7.
- Amiodarone, class 1C agents, and sotalol were associated with less AF recurrence compared to dronedarone, with hazard ratios of 0.58,0.70, and 0.79, respectively 6.
- Dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm, with a failure rate of 75.1% versus 58.8% 4.