Main Research Findings

Dronedarone is a class III antiarrhythmic drug that has been used to manage atrial fibrillation in humans ( 22 ). Research has shown that dronedarone can decrease heart rate, reduce cardiac output, and increase systemic vascular resistance ( 22 , 21 ). This drug also has a negative effect on cardiac inotropy and lusitropy, meaning it can weaken the heart’s ability to contract and relax properly ( 22 ). Dronedarone may also have anticoagulant and antiplatelet effects, potentially contributing to its observed reduction in stroke and transient ischemic attacks in patients with atrial fibrillation ( 18 ). However, it’s important to note that the long-term effects of dronedarone are not fully understood, and further research is needed to assess its safety and efficacy.

A study comparing amiodarone and dronedarone in a rabbit model found that both drugs slowed heart rate and reduced heart rate variability ( 15 ). However, only amiodarone had a negative effect on cardiac contractility and reduced cardiac dyssynchrony ( 15 ).

Research suggests that dronedarone may have more potent anti-atrial fibrillatory action and a wider cardiovascular safety margin than amiodarone ( 11 ). This is due to the deuteration of dronedarone, which reduces the inhibition of sinus automaticity and prolongs the atrial effective refractory period while maintaining blood pressure and ventricular rate stability ( 11 ). Additionally, the deuterated analogue of dronedarone, called poyendarone, has shown a similar antiarrhythmic effect but with reduced beta-adrenoceptor blocking activity and cardiosuppressive effects compared to dronedarone ( 13 ).

Dronedarone has been found to be more effective than amiodarone in inhibiting small conductance calcium-activated potassium channels (SK) in patients with chronic atrial fibrillation ( 12 ). This suggests that IKAS could be a potential target for amiodarone and dronedarone in the management of chronic atrial fibrillation ( 12 ). However, dronedarone can inhibit cytochrome P450 2J2 (CYP2J2) and soluble epoxide hydrolase (sEH) enzymes, which are involved in the metabolism of arachidonic acid to cardioprotective epoxyeicosatrienoic acids (EETs) ( 19 ). This inhibition can lead to cardiac mitochondrial toxicity, which can be rescued by EET enrichment ( 9 ).

Benefits and Risks

Benefit Summary

Dronedarone is a drug used to manage atrial fibrillation. It has been shown to be effective in maintaining sinus rhythm, reducing the ventricular rate during arrhythmia recurrence, and lowering heart rate and blood pressure (, 3 ). Furthermore, dronedarone is a non-iodinated benzofuran derivative that was developed as a potentially less toxic alternative to amiodarone ( 1 ). Studies have shown that it appears to be devoid of some of the side effects associated with iodine in amiodarone ( 1 ).

Risk Summary

Dronedarone can have a negative impact on cardiac function, reducing the heart’s ability to contract and relax properly ( 22 , 21 ). Furthermore, it can increase systemic vascular resistance, potentially leading to complications ( 22 ). Dronedarone has been associated with risks of liver toxicity ( 8 ), thyroid dysfunction, and pulmonary toxicity (). Therefore, it is important for patients to discuss the potential benefits and risks of dronedarone with their doctor before taking the drug. The drug is not recommended for patients with impaired cardiac function ( 22 ).

Comparison Between Studies

Commonalities

Multiple studies have found that dronedarone can impact heart rate, cardiac function, and electrical activity. They also have shown that it may be effective in treating atrial fibrillation. However, it’s important to note that these studies have used different methods and patient populations, which may explain the variations in results observed.

Differences

Studies have found that dronedarone may have a wider safety margin and more potent anti-atrial fibrillation action than amiodarone. This is partially attributed to the deuteration of dronedarone ( 11 , 13 ). However, further research is needed to confirm these findings, as the long-term effects of dronedarone are not fully understood.

Consistency and Contradictions in Results

While the studies consistently point to the potential benefits of dronedarone in treating atrial fibrillation, they also highlight the potential risks. These risks include negative effects on cardiac function and potential for liver toxicity ( 8 ). Additionally, research suggests that its effects can vary significantly depending on the individual ( 5 , 24 ).

Points to Consider When Applying These Findings in Real Life

Dronedarone is a potentially effective medication for treating atrial fibrillation. However, due to its potential side effects, it is essential to carefully consider the risks and benefits with your doctor before taking it. It is crucial to take it according to your doctor's instructions to minimize risks.

Limitations of Current Research

Current research on dronedarone has several limitations. First, the long-term effects of dronedarone are not fully understood. More research is needed to assess its long-term safety and efficacy. Second, many studies have been conducted on relatively small populations, which may not reflect the diversity of patients who could benefit from dronedarone.

Future Research Directions

More research is needed to better understand the long-term effects of dronedarone. It would be beneficial to investigate the impact of dronedarone on different patient populations and to conduct larger-scale studies that account for potential individual variations in response to the drug. Furthermore, ongoing research into the development of safer and more effective antiarrhythmic drugs is important.

Conclusion

Dronedarone is a medication that has shown promise in treating atrial fibrillation, but it is important to weigh the benefits against potential risks. More research is needed to fully understand its long-term effects and to develop safer and more effective antiarrhythmic medications. It’s important to have open conversations with your doctor to discuss the potential benefits and risks of this drug. They can help you make informed decisions about your treatment plan.