Experts Argue the Pros and Cons of Multaq (dronedarone) as a Treatment for Atrial Fibrillation

By Mellanie True Hills and Peggy Noonan

  • Summary: As explores the controversy surrounding Multaq (dronedarone), we see what some experts have said to help patients put this information into context
  • Aproximate reading time: 5–7 minutes

August 9, 2011

As we reported in our companion piece on Multaq, What Do We Know About Multaq (dronedarone) for Atrial Fibrillation, there’s been a lot of hype both for and against Multaq, the new drug that was designed to provide the same benefits as amiodarone with fewer risks. That article examined Multaq’s pros and cons by sifting through reports of problems and possible hazards that have been linked to the drug. Our goal was to help people with afib make their own judgment about Multaq.

Now, in this article, we’re narrowing our focus to concentrate on what some experts have said about Multaq. Again, we’ll explore some of the negative and positive points experts have raised and put them into context from a patient’s perspective so you can decide what’s right for you.

When a new medicine is developed, it takes time and research to sort out all its benefits and risks, and to gain a clearer picture of which patients may benefit from taking it.

Weighing any drug’s risk-to-benefit ratio can be complicated. That’s why people with afib, their caregivers, and their doctors and other health care providers need to keep up with the latest research.

Doctors and patients need to consider questions such as:

  • Will the new drug work better than the medicine or medicines the patient is currently taking?
  • Is the new drug likely to have negative interactions with any medications the patient is already taking?
  • Does the new drug pose fewer risks or more tolerable risks than other old or new medicines?
  • Does it offer a new treatment approach that may be more helpful for this patient than other drugs or other medicines the patient has already tried?
  • Would the new drug be a sufficiently better choice for this patient—considering his or her overall health, other medications, other conditions, and other factors—to merit changing from current treatment?

The opening salvo from those concerned about Multaq came in an April 2010 article, Dronedarone for Atrial Fibrillation: Have We Expanded The Armamentarium?, in the Journal of the American College of Cardiology (JACC). Dr. David Singh, Dr. Sanjay Kaul, and their co-authors expressed concern over Multaq. They questioned the design of the trial that led to Multaq’s approval and raised three key issues—efficacy, safety, and timing, or when Multaq should be used in managing afib patients.

Of interest is that one of the co-authors, Dr. Kaul, actually voted in favor of Multaq as a member of the FDA Advisory Committee that recommended that the FDA should approve it.1

Let’s look at the three primary issues the JACC article raised: safety, efficacy and when to try Multaq.

Multaq’s Safety and Efficacy

In pointing to pooled data from six dronedarone trials, Dr. Singh said, “These data suggest that dronedarone has modest antiarrhythmic efficacy (effectiveness),” and that it is only half as effective as amiodarone. He conceded that Multaq may “lower the risk of some clinical outcomes” (clinical outcomes are health status changes in those who took the medication), but that the relatively modest efficacy in preventing recurrence of atrial fibrillation and atrial flutter makes the drug’s role in the management of afib and atrial flutter “uncertain.”

Singh also expressed skepticism about the drug’s role in managing atrial fibrillation due to “questions regarding its short-term and long-term safety in at-risk patients.” This refers to the ANDROMEDA trial (Antiarrhythmic Trial With Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease), which was stopped early due to deaths in this high-risk population.

It is worth noting that the ANDROMEDA trial wasn’t an atrial fibrillation trial—it was a heart failure trial—and thus would not apply to the vast majority of atrial fibrillation patients as they are at much lower risk. Singh indicated that the ATHENA trial (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death From Any Cause in Patients With Atrial Fibrillation / Atrial Flutter) was a subsequent trial “to define a population for which dronedarone may be safely used.”

However, Dr. Christian Torp-Pedersen, a member of the steering committee of the ANDROMEDA and ATHENA trials, and his coauthors argued that the ATHENA trial demonstrates Multaq’s safety. In their commentary in the same April 2010 issue of the Journal of the American College of Cardiology, Antiarrhythmic Drugs: Safety First, they stated that ATHENA “is the first large trial to provide safety data in a moderate risk population that comprises a large part of the relevant patients for rhythm control therapy.”

On efficacy, Dr. Torp-Pedersen agrees that the evidence shows that Multaq does not work as well when compared to its predecessor, amiodarone, and that Multaq is “clearly less efficacious in maintaining sinus rhythm,” and he pointed out that this is true of all antiarrhythmic medications.

Where Does Multaq Fit for Managing AF Patients?

Singh argued that “treatment with antiarrhythmic drugs should generally be considered only when symptoms persist despite adequate rate control” and that “the available data support only limited use of dronedarone for select patient populations, mostly as a second- or third-line agent in lieu of amiodarone” after other rhythm control medicines with a longer track record such as flecainide and sotalol have been tried.

But Torp-Pedersen countered that comparing dronedarone with flecainide, sotalol, or other drugs on the market, as Singh and his coauthors did, “is futile because there are no comparable trials, and comparison with historical data is often misleading.”

Another rebuttal to the Singh article was published in the Letters to the Editor column in the October 2010 issue of the Journal of the American College of Cardiology. In that correspondence, Dr. Stuart J. Connolly and Dr. Stefan H. Hohnloser said, “The meta-analysis presented by Singh et al of 6 dronedarone trials suffers from errors in methodology and accuracy. One of those errors was that “Inclusion of 1 trial of patients with heart failure together with 5 trials of patients with AF introduces needless heterogeneity, especially because dronedarone is indicated only for AF.”

They noted that “The findings of the ATHENA trial are unique in antiarrhythmic drug therapy” and “for the first time, an antiarrhythmic drug has been shown to have an important impact on cardiovascular outcomes.”

Now, they concluded, doctors don’t have to settle for simply suppressing afib; they have a promising way to improve patient outcomes via antiarrhythmic therapy.

Bottom Line

The final word comes from the three afib guidelines committees, none of whom seemed to have agreed with Singh that dronedarone should be second- or third-line treatment for afib. In the latest afib guidelines, all of the guidelines committees placed dronedarone higher, and in most cases as a first-line treatment for afib where applicable. Notably, Multaq doesn’t require hospitalization in order to start patients on the drug, as many of the others do.

Comments:Unfortunately, while the Singh article received extensive coverage in the media, these subsequent articles did not. As a result, most patients were left with unfounded questions and concerns about Multaq. So when you read articles that concern you, please do not jump immediately to conclusions. If it applies to you, first look to see where the writer is coming from, and then please do your homework and discuss your findings with your doctor. Don’t let any journalist, including us, dictate your decisions about medications or procedures.

Finally, so that you know where we are coming from, remember that the afib community is our number one priority. As someone who has lived with afib, and knows what it does to you, Mellanie’s mission is to give you credible, factual, and balanced information to help you do your research and make your own decisions. We’re not trying to give you answers, but to give you facts so that you can make the best decision for you.

The maker of Multaq is one of many organizations that has contributed so that we can do research and writing to give you the best content, but they have no input into that content unless we specifically ask them for comments or clarifications and what is written is our own. Please remember that those who contribute to DO NOT get favored treatment. You come first, and therefore we have covered the facts, good and bad, here in these two Multaq updates.

If you haven’t already, see the companion Multaq article to this one, What Do We Know About Multaq (dronedarone) for Atrial Fibrillation.

To learn more:

1 Stiles S. FDA advisory panel recommends dronedarone approval for atrial fib Arrhythmia/EP, March 20, 2009