What Do We Know About Multaq (dronedarone) for Atrial Fibrillation

By Mellanie True Hills and Peggy Noonan

Summary: In light of recent news about the use of Multaq (dronedarone) for atrial fibrillation, it’s time to put into context for patients what has transpired in the two years since FDA approval.

Aproximate reading time:  15–20 minutes

August 9, 2011

It has been two years since the US FDA approved Multaq® (dronedarone) for patients with atrial fibrillation or atrial flutter. This US approval started a cascade of approvals around the globe, and Multaq has since been added to most afib guidelines, though getting the cost covered is an issue in some places.  (For help in the US, visit the MULTAQ Reimbursement Hotline.)

Multaq was designed to be a safer antiarrhythmic drug than its predecessor, amiodarone, and is an analogue (same type of chemical compound) of amiodarone that was structurally modified to reduce the risks of toxic side effects.1 Approximately one million prescriptions for Multaq were dispensed between July 2009 and June 2011, and some 241,000 patients filled Multaq prescriptions at retail pharmacies in the US, according to the FDA.2

As a patient, you have probably seen lots of hype-filled reports—both positive and negative—about Multaq, and about lots of other drugs for that matter. When a drug is approved, there’s an inevitable blitz of hype followed by a barrage of negative publicity. The negative reports sometimes scare people away from new medications that could help them. Often these articles are written by folks who mean well, but simply don’t understand what it is like to live with afib and may not have the best interests of patients at heart. We need to look at where they are coming from and whether they are even qualified to advise us as patients as we seek to make decisions that are best for us.

In this article, we will look at some of the positive and negative things that have been written about Multaq, or that we have learned about it, and put them into context from a patient’s perspective. We will also examine new information that has been released almost daily as we have tried wrapping up this article.

The debate began in April of 2010 when Dr. David Singh, Dr. Sanjay Kaul, and their co-authors expressed concerns about Multaq. We examined and discussed those concerns in detail in Experts Argue the Pros and Cons of Multaq (dronedarone) as a Treatment for Atrial Fibrillation, a companion piece to this article.

Then, in November, 2010, another publication, the Institute for Safe Medication Practices QuarterWatch: 2010 Quarter 1 Monitoring MedWatch Reports reported some of the first post-approval problems linked to Multaq. Let’s explore the key points it raised.

QuarterWatch Concerns

An important note for women: QuarterWatch reported that Multaq-linked birth defects had been found in animal studies and therefore Multaq has been classified as a pregnancy Category X drug whose risks outweigh the benefits during pregnancy. This means thatwomen who are pregnant, or plan to become pregnant, should not take Multaq.

QuarterWatch reviewed a total of 33,046 adverse events, or problems caused by various medications, that were reported to the FDA during the first quarter of 2010. Of that total, Multaq was named as the primary suspect in 387 reports of serious events, including 24 deaths, 2 disabilities, and 361 other serious adverse events. However, QuarterWatch was very clear in stating that“submission of an individual report does not in itself establish that the suspect drug caused the event described — only that an observer suspected a relationship.”

That Quarter 1 report concluded that Multaq may:

  • cause or worsen heart failure,
  • trigger potentially lethal irregular heartbeats,
  • impair kidney function, and
  • interact with other drugs

Let’s take a closer look at each of these issues.

Heart Failure

In 2005, the ANDROMEDA clinical trial of Multaq in patients with heart failure but no atrial fibrillation was stopped because Multaq doubled the risk of death due to worsening of the existing heart failure. But in the ATHENA clinical trial in which participants had atrial fibrillation but minimal or no heart failure, Multaq “reduced cardiovascular hospitalizations by 24% but had no statistically significant effect on mortality [death],” according to the QuarterWatch report. Since approval, 100 new or worsened heart failure cases have been reported. The Multaq Medication Guide says the drug should not be taken by anyone who has severe heart failure, or by people who have recently been hospitalized for heart failure, even if their condition improved. And the Multaq prescribing information now cautions doctors to consider stopping Multaq if heart failure develops or worsens.

Comments:These heart failure cases are definitely a concern. Multaq was not approved for people who have serious heart failure, but the new cases of heart failure in people on Multaq is a big concern.

But one has to wonder if the heart failure was caused by Multaq or by the afib. Were these patients already heading into heart failure before starting Multaq? The afib guidelines allow those with no afib symptoms to be left in afib long term, which can bring on heart failure. (See Atrial Fibrillation: The Patient Perspective to Better Care for more information.) Or perhaps in some, the Multaq just wasn’t working, so did the Multaq cause the heart failure or did their afib cause it? We just don’t know. That’s an area needing further study.

Irregular Heartbeat

Reports of irregular heart rhythms on Multaq included 18 “potential” cases of bradycardia (abnormally low heart rate), 47 cases of atrial tachycardia (fast atrial heartbeat) and 13 cases of ventricular tachycardia (fast ventricular beats).

Comments: The total number of adverse events reported for Multaq could be skewed if one event was reported more than once, or by multiple people, or to multiple recipients. How could that have happened?

I am willing to accept some of the blame for this. When I received early reports of serious issues from specific afib patients, I reported those adverse events directly to Multaq’s manufacturer, sanofi-aventis. To protect patient privacy, I never reported any individual patient names in these reports. Sanofi was very diligent about making sure I had all the right forms to report these incidents and also asked me to ask these patients to report their events in detail or to ask their doctors to do so, to be sure no detail was overlooked.

Some of these reports could have been sent directly to the FDA while others may have been sent to Sanofi, or to both. The company, in turn, was required to report all discrete events to the FDA, so it’s possible that the FDA database of adverse events could contain events that were double- or triple-counted. In fact, QuarterWatch specifically mentions this problem, saying that the FDA system was flooded with duplicate reports taken from the same sources because the FDA requires companies to monitor the literature and report from it. Since I didn’t report patient names, there is no way to know if my reports were duplicates, so I take some responsibility for potential redundant data and over reporting.

Thus we can’t know for sure how many events actually occurred of each type below, so please consider that these adverse events could be much more rare than the numbers below indicate.

  • Bradycardia

I personally reported several cases where people who were started on Multaq ended up in the ER with bradycardia. Two were already taking beta blockers and their doctors did not decrease or discontinue these drugs when starting Multaq. Since Multaq has beta-blocking properties, those patients wound up being double-dosed. One of those cases occurred because the doctor was not there when the Multaq representative came to train the doctors in the practice. That case was clearly not the fault of the drug.

I suspect this is far from being an isolated incident, and as soon as I discovered what happened in those initial two cases, I alerted the afib community to be aware of this risk and to raise this issue with their doctors when Multaq was prescribed. I have continued to sound this alarm.

I suspect that most of the bradycardia was due to similar circumstances. So while this issue is being blamed on Multaq, the fault clearly lies with mistakes by the prescribing doctor.

  • Atrial Tachycardia

Is it possible that some of the 47 cases of atrial tachycardia were breakthrough arrhythmias, not adverse events? These could simply be cases in which Multaq didn’t work, not unlike with other antiarrhythmic drugs. Amiodarone is the most effective antiarrhythmic drug, yet it only works about half the time. So was the arrhythmia already there or did the drug actually cause it? I don’t know how we would know.

Since some afib drugs can be pro-arrhythmic in some patients, notably beta blockers, we have to consider whether it’s Multaq’s beta blocking properties that caused the problem. It is widely reported in the afib community that those with vagally-mediated afib should not take beta blockers because for those patients, beta blockers may be pro-arrhythmic. This could apply to Multaq as well.

  • Ventricular Tachycardia

The 13 cases of ventricular tachycardia are of great concern, but it must be noted that ventricular issues are very common with many antiarrhythmic drugs. That’s why doctors must admit patients to the hospital for several days to start many antiarrhythmic drugs, though not Multaq. While this is a very small number of cases in the greater scheme of things, it is nonetheless something to be aware of if you start Multaq.

Between the potential for gastric upset among some small percentage of those starting Multaq, and the very small potential for other rhythm issues, it seems appropriate to not start Multaq when you have big plans, such as a trip or family event. Perhaps it is a good idea to plan to be home for 2-3 days upon starting it to make it easy to address any issues that might arise.

Kidney Function

The QuarterWatch article notes that 15 cases of kidney failure (4 acute) or kidney impairment were reported but says there was not enough detail to fully evaluate the cases. It speculates that if there is a connection, it might be as a result of Multaq’s effect on heart failure or its effect on other drugs. For example, Multaq can increase the level of cholesterol-lowering medicine, and too much of that medication can increase the risk of kidney failure. In addition, heart failure can lead to kidney failure.

People who took Multaq had higher blood levels of creatinine, which normally would indicate a problem with kidney function. However, the maker of Multaq contends that even though the drug raised creatinine levels, “it did not otherwise reduce kidney function.”

Drug Interactions

Multaq’s interaction with other drugs, called a “contraindication,” was flagged as a major safety issue by QuarterWatch. That report noted problems with “many, many different drugs,” including cholesterol-lowering medications and some medications used by people who have atrial fibrillation and atrial flutter, such as digoxin and warfarin. We have subsequently learned that there can also be some interaction with Pradaxa, which will be addressed later in this article.

The FDA recommends that people who take Multaq talk with their doctor and pharmacist about other medicines they’re taking, including prescription drugs and over-the-counter medicines, vitamins and herbs.

The FDA Multaq Medication Guide cautions against using Multaq for people who take any of these medicines:

The Multaq Medication Guide also warns: “Do not drink grapefruit juice while you take Multaq” because grapefruit juice can increase the amount of Multaq in the bloodstream and increase risk of side effects.

QuarterWatch’s “safety signals” on Multaq continued in the next issue, Institute for Safe Medication Practices QuarterWatch: 2010 Quarter 2 Monitoring MedWatch Reports, and included a large number of drug interactions:

“With nine different contraindications and numerous interactions with other drugs, we saw additional evidence of serious injury associated with apparent medication errors. One of the most potentially important of those contraindications was a warning not to use dronedarone with other drugs (or even herbal products) with an effect of slowing electrical conduction in the heart. This prohibition would include most other antiarrhythmic drugs. Despite this contraindication, we identified 39 cases since approval where patients were seriously injured (including 4 deaths) while taking other contraindicated antiarrhythmic drugs, specifically amiodarone and sotalol. We also found 16 reports of injuries mentioning off label use, 12 cases of drug interactions and 15 cases of dosing or administration error.”

Comments: Were these cases in which doctors just weren’t paying sufficient attention or cases of different doctors prescribing contraindicated medications? It is possible that the patient or family members failed to mention other drugs they were taking that should not be taken with Multaq. This is one more reason for patients to keep an updated list of their medications, the amount taken, and the frequency, and to share that with their doctors at every visit.

While these are adverse events, they are medication errors due to improper prescribing or use and are not directly the fault of the medication.

Pradaxa and Multaq

We previously reported on Pradaxa (dabigatran) in October 2010 in FDA Approves Pradaxa as Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation. This new anticoagulant drug may be taken by people with afib who are also taking Multaq, so Sanofi Aventis has added new information to the drug interactions section (7.3) of its Multaq Highlights of Prescribing Information. A study conducted by Sanofi indicated that patients taking Multaq and Pradaxa may be exposed to higher than intended amounts of Pradaxa, which may be increased by 1.7 to 2-fold (doubled). Is that bad? It’s too early to say. As Sanofi notes, “The clinical implications of this drug interaction are unknown.”

Comments:In discussions with top afib doctors about Multaq and Pradaxa, it was suggested that patients should take these two drugs a couple of hours apart. If you’re on both, please remember to discuss how to handle this with your doctor.

Whether the drug is Pradaxa or any other medication, the bottom line for patients boils down to this: Talk with your doctor about the medicines you’re taking or considering taking. And if you already take Multaq, Sanofi says you should not interrupt treatment without seeking advice from the physician who prescribed Multaq for you.

Liver Hazard Concerns

Early in 2011, a new Multaq issue raised concerns about whether the drug caused liver damage. To address this issue, Sanofi and the FDA simultaneously released a “matched pair” of documents on January 14. Both documents advised health care providers there had been two cases of acute liver failure that led to transplant, and although cases of severe liver injury were rare, the FDA and Sanofi advised providers to check patients’ liver enzymes periodically, especially during the first few months of taking Multaq. Will this prevent patients taking dronedarone from developing severe liver injury? That answer “is not known,” the FDA’s advisory said.

  • Liver disease tests screen for and detect damage to the liver, assess the severity of damage, and help to identify what’s causing liver injury.

The liver hazard announcements reminded health care providers—and patients—to report any symptoms of liver injury or toxicity, such as anorexia (loss of appetite), nausea, vomiting, fever, malaise (feeling unwell), fatigue, pain in the upper right quadrant (upper right side of the body, behind the rib cage), jaundice, dark urine, and itching.

The Data Summary section of the FDA Drug Safety Communication described the two women who needed liver transplants: both were approximately 70 years old and both previously had normal liver enzyme tests.

  • One had taken dronedarone for four and a half months. She had “underlying intermittent atrial fibrillation, arterial hypertension and stable coronary artery disease,” the report notes, and her pre-transplant workup did not indicate any other cause of liver failure.
  • The second had taken dronedarone for six months. She had a medical history of paroxysmal atrial fibrillation and Sjogren’s syndrome (a chronic autoimmune disease in which the body attacks itself). She developed liver damage symptoms after being treated with dronedarone for six months and received a liver transplant one month later and her pre-transplant workup also failed to show any other cause of liver failure.

    As the safety communication points out, “Because these reactions are reported voluntarily from a treatment population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.”

    Sanofi’s letter, Important Drug Warning: Hepatic Failure in Patients Treated with Multaq (Dronedareone), January 14, 2011, also recommended that healthcare professionals advise their patients to report symptoms suggestive of liver injury. Doctors should consider periodic liver enzyme tests in Multaq patients, and if any injury was found, Sanofi recommended appropriate treatment and investigation to find what caused the liver damage. If other explanations for liver injury were not found, it advised doctors not to restart Multaq in those patients.

    “We encourage you to discuss the new important safety information outlined in this letter with your patients,” Sanofi wrote. The letter closed with a recommendation that healthcare providers report any cases of liver injury or failure or serious adverse event in which Multaq was suspected, and provided contact information for reporting to Sanofi or the FDA.

    Similar warning letters were issued by health regulatory agencies in the United Kingdom3 and Europe4 on January 21, 2011.

    Comments: Both kidney toxicity and liver toxicity are common with amiodarone, so a signal of some cases of the same toxicity with dronedarone could indicate there is a similarity in the two drugs caused by some factor other than the iodine moiety – part of an iodine molecule – that was removed from amiodarone to create dronedarone. But we don’t know enough from the dronedarone reports. Were any of the patients who had kidney or liver toxicity previously on amiodarone?

    Though the reports on both of the transplant patients indicate that their workups failed to show any other cause of liver failure, we still have to wonder if there were other drugs that either one had been taking, or had previously taken, and maybe that weren’t even mentioned to their doctors, that could account for or contribute to this. And could they have previously been on amiodarone? If they were and their medication was switched from amiodarone to dronedarone, could latent damage from amiodarone be to blame for the toxicity and not dronedarone?

    And what other factors might have affected the transplant patients’ liver health? Could other medical conditions (in addition to afib) increase the risk of toxicity? Or could other medications be a factor? And how large a role might diet and lifestyle play? We already know, for example, that people with afib are generally advised to limit alcohol consumption. Perhaps people who take Multaq need to be especially prudent.

    FDA Letter to Sanofi Was Not Directly Related to Multaq

    On January 28, 2011, the FDA issued a Warning Letter to Sanofi-Aventis regarding problems with the company’s compliance with FDA Postmarketing Adverse Drug Experience (PADE) reporting requirements on Multaq and other drugs.

    When we heard about that letter, we asked Sanofi for clarification for patients who might be using Multaq or other drugs from the company and they shared a response with us. It is important to note that the FDA Warning Letter was about reporting processes and timeframes involved in the reporting requirements for adverse drug events and was not about the safety of any Sanofi products.

    In communicating with us, the company stated:

    “Patient safety is a priority at sanofi-aventis. We remain committed to the efficacy and safety profile of Multaq® (dronedarone) and its treatment of appropriate patients. We continue to work with the FDA and health authorities around the world to provide healthcare professionals with current information on all our medicines to make informed choices about treatment options for their patients.”

    That includes issuing updates, like the heart failure and liver damage and failure updates described in this article, and making sure those updates are communicated to health care professionals and patients.

    What Is the Latest Info?

    In June of 2011, Multaq appeared again in MedWatch, FDA Safety Information Update on Multaq, which reported: “Postmarketing cases of interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported.” This means the FDA will study Multaq to decide whether the drug caused the event, and if so, whether regulatory action such as revising the label is needed.

    In July of this year, Sanofi announced the suspension of the PALLAS (Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of standard therapy) clinical trial due to increased cardiovascular events in those patients on Multaq. (The term “cardiovascular events” covers any incident that causes damage to the heart muscle.)

    The drug is generally approved for those with paroxysmal (intermittent) or persistent (continuous) atrial fibrillation, or for those preparing for a cardioversion, but the PALLAS trial looked at a different patient population. Participants in PALLAS had permanent atrial fibrillation, meaning that there was no intent to put them back into sinus rhythm. They also had at least one other cardiovascular disease risk factor.

    Sanofi’s July 7, 2011 press release, Sanofi Provides Multaq® Phase IIIb PALLAS Trial Update, reported that trial investigators had been asked to get in touch with patients in the trial to have them stop taking dronedarone, but noted that patients not in the trial should not stop taking it and should consult their doctors. The press release also clearly stated that the trial was not stopped due to any liver issues.

    Dr. Stuart Connolly (McMaster University, Hamilton, ON), PALLAS co-primary investigator, said in Dronedarone trial suspended due to CV events in permanent atrial fibrillation that there was a significant increase in risk of major cardiovascular events (stroke, heart attack, clot, or cardiovascular death) in PALLAS. He also stressed the differences in the two trial patient populations:

    • In PALLAS, patients were very high risk, having had a stroke or heart attack, or a low ejection fraction (indicative of heart failure), and were in afib all the time. These patients saw no reduction in afib.
    • In ATHENA, the trial that led to approval of dronedarone, patients were in intermittent (non-permanent) afib and had mild risk factors such as high blood pressure or age greater than 75. These patients experienced reductions in afib from being on Multaq and had fewer hospitalizations for afib.

    On July 21, 2011, both the FDA and the European Medicines Agency announced reviews of Multaq in light of the suspension of the PALLAS clinical trial.

    The FDA Drug Safety Communication: Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events announced that the FDA was reviewing the data from the trial and provided additional insight into the adverse cardiovascular events in PALLAS. The number of heart attacks (myocardial infarctions) was the same whether patients were taking Multaq or placebo (three in each of the two groups), but other factors were dramatically higher in those taking Multaq. (The first two results below were co-primary endpoints, meaning two or more had to occur.)

    • Heart attacks, strokes, clots, and other cardiovascular deaths: 32 in Multaq patients vs. 14 in placebo patients
    • Unplanned (cardiovascular) hospitalizations or deaths: 118 vs. 81
    • Deaths: 16 vs. 7
    • Strokes: 17 vs. 7
    • Heart failure hospitalizations: 34 vs. 15

    The European Medicines Agency (EMA), which had already announced in January when the liver damage reports came out that it intended to review use of Multaq, announced in European Medicines Agency updates on ongoing benefit-risk review of Multaq a broadened scope of its review to include assessment of the new PALLAS information, with results expected in September.

    Both FDA and EMA announcements reminded prescribers to follow current (existing) recommendations for Multaq use, which means not prescribing Multaq to patients with permanent atrial fibrillation and to monitor patients to make sure they do not progress into permanent atrial fibrillation. Patients currently taking Multaq were also advised “not to stop their medication without consulting their doctor”.

    Once these official reviews are complete, various guidelines will be reviewed and revised as necessary. In a press release, European Society of Cardiology (ESC) announces review of Atrial Fibrillation Guidelines, the ESC advised that:

    “Both the EMA and FDA have advised that the use of dronedarone should be restricted to the approved indications, and that dronedarone should not be used in patients with permanent atrial fibrillation. The ESC Guidelines are consistent with this advice. The ESC will produce a focused update of the AF Guidelines when the full results of PALLAS have been published and regulatory authorities have revised the labeling for dronedarone.”

    Comments: It is important to reiterate that if you are currently on Multaq for paroxysmal or persistent atrial fibrillation, or taking it in preparation for a cardioversion, and you are doing well, then you should not stop Multaq as the PALLAS study does not apply to you. But you will want to make sure that your doctor continues to monitor you. And it is important to realize that all rate and rhythm control drugs have side effects, so Multaq is not unique in this regard.

    We know that being in permanent atrial fibrillation is already risky, with a higher risk for heart failure, heart attacks, and stroke. Whether or not Multaq played a role in these events is unknown, though we do know that those who already have severe heart failure should not be given Multaq.

    There is some evidence to indicate that long term afib not only can lead to heart failure, but also that higher amounts of fibrosis (scarring) due to long term remodeling from being in afib correlates with strokes. Because of these longer term risks, we are not big fans of leaving folks in afib long term. You might wonder if some of these risks were built up from being in afib long-term and could have influenced the outcomes of the PALLAS trial. Very possibly.

    What Is the Good News about Multaq?

    Studies have shown that Multaq is safer than amiodarone5, which is very commonly given and is currently the most effective drug for controlling or stopping afib. Many patients refuse to take amiodarone because of its serious side effects, so Multaq offers a safer alternative.

    Comments: It’s not unusual to have many adverse event reports due to the heightened vigilance that accompanies the introduction of a new drug. In this case, Multaq, as a derivative of amiodarone, is reflecting a similar level of side effects, though seemingly less severe, than the drug from which it was derived. One study estimated that for every thousand patients treated with Multaq instead of amiodarone, there would be approximately 228 more AF recurrences in exchange for 62 fewer adverse events and 9.6 fewer deaths.5

    Those who focus on the negatives of Multaq don’t seem to get upset that amiodarone has these kinds of adverse events, and much worse. And amiodarone is prescribed off-label, meaning that the FDA has not approved it for afib.

    It seems that these alarms are raised for brand drugs, not generics. As you can see, it’s not always the drug that is at fault. Sometimes it is the doctor or the system.

    So please be a discriminating reader. The next time you read an article by someone who is bashing an afib treatment, don’t panic—just look at what else they have done to identify their intent. In most cases, they haven’t walked in our shoes, so they really cannot understand our needs and they do us a disservice by providing biased reports. My fear is that with so few medication options, some patients are skipping afib treatments that might work well for them simply because they have been scared off by carelessly-researched articles or scare tactics. Thus I worry about the potentially needless afib and strokes that may result.

    We need to look at all sides of the question and carefully examine the data The bottom line is that these are important issues to consider, but do not jump to conclusions based solely on what you read in the popular press. Do your homework, and look for reputable sources. And then have a conversation with your doctor to determine whether the new information should change your course of treatment.

    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. In the case mentioned in this article, we specifically requested information about the FDA letter, but what we wrote was our own. Please remember that those who contribute to StopAfib.org DO NOT get favored treatment. You come first, and therefore we have covered the facts, good and bad, here in these two Multaq updates.

    UPDATE:

    We’d like to give you more good news about Multaq that just came out. In a post hoc analysis of the results of the ATHENA trial published in Europace, Impact of dronedarone on hospitalization burden in patients with atrial fibrillation: results from the ATHENA study, Dr. Christian Torp-Pedersen, a member of the steering committee of the ANDROMEDA and ATHENA trials, and his coauthors found Multaq patients had “significantly” fewer cardiovascular hospitalizations than patients who took placebo. Hospitalizations for acute coronary syndrome (coronary heart disease) were reduced, with 71 for Multaq patients compared to 113 for those on placebo, and fewer associated hospital days (816 on Multaq; 1,188 on placebo).

    Multaq patients had fewer first cardiovascular hospitalizations (675) than those on placebo (859) and fewer hospitalizations for afib — 514 vs. 829. That means, as MedPage Today reported, Multaq patients had 26% fewer first cardiovascular hospitalizations and nearly 40% fewer hospitalizations for atrial fibrillation than placebo patients. “This is an important finding” because cardiovascular hospitalization “is a valid surrogate endpoint for mortality (death) in studies of Afib,” the study authors note. Other important information from the study includes the following:

    “ATHENA is the only study powered to demonstrate a clinical benefit beyond maintenance of sinus rhythm specifically in patients with AF.”

    “This reduction in AF-related hospitalizations was not simply due to fewer cardioversions, but also due to a decrease in the severity of recurrent AF episodes.”

    “Treatment of patients with paroxysmal or persistent AF or AFL with dronedarone is associated with a marked reduction in the number and duration of CV hospitalizations, particularly those associated with potentially life-threatening conditions.”

    Comments: This is good news for all who have afib, but especially for those who also have heart disease, which is a significant percentage of the afib population. For those patients, rhythm medication options are often limited because some afib drugs can lead to dangerous ventricular rhythms. Multaq appears to be one of the safer medications for those with heart disease, and it is especially good news that this study showed fewer hospitalizations and shorter hospital stays for acute coronary syndromes.

    If you haven’t already, see the companion Multaq article to this one, Experts Argue the Pros and Cons of Multaq (dronedarone) as a Treatment for Atrial Fibrillation

    To learn more about Multaq, see:

     

    1 Penugonda N, Mohmand-Borkowski A, Burke JF. Dronedarone for atrial fibrillation: How does it compare with amiodarone? Cleveland Clinic Journal of Medicine 2011 78(3) (March 2011): 179-185 doi:10.3949/ccjm.78a.10049

    2 FDA. Drug Safety Communication: Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events, July 21, 2011

    3 MHRA (Medicines and Healthcare products Regulatory Agency) New information on possible risk of liver injury with dronedarone (Multaq) Safety warnings and messages for medicines. 21 January 2011

    4 European Medicines Agency. 21 January 2011. Questions and answers on the possible risk of liver injury with Multaq (dronedarone)

    5Piccini JP, Hasselblad V, Peterson ED, Washam JB, Califf RM, Kong DF. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. Journal of the American College of Cardiology. 2009 Sep 15;54(12):1089-95)