Experts disagree on when to use dronedarone (Multaq)

The billion dollar question is this: when to use Multaq (dronedarone)? A new viewpoint and commentary in JACC from Sanjay Kaul’s group (Singh et al) offers a highly conservative answer to the question. An accompanying editorial by Christian Torp-Pedersen, Ole Dyg Pedersen, and Lars Køber provides a much more liberal view of the drug.

It all comes down to different ways of interpreting the safety and efficacy data. Surprisingly, both groups agree that dronedarone is less effective than amiodarone as an antiarrhythmic drug, and both agree that dronedarone is safer than amiodarone in the indicated population of low and intermediate risk patients. And both agree that dronedarone should not be used in high risk patients (unstable NYHA class 3 and class 4 HF patients).

Singh et al get with the guidelines and write that “it is difficult to support an approach to rhythm control in most patients with AF without first trying a rate-control strategy.” Once a rhythm-control strategy is adopted, however, they argue that dronedarone should generally be used as either a second- or third-line agent. (They then offer a detailed flow chart for treatment choices based on the clinical characteristics of the patient.)

They conclude:

Although we recognize that reconciling efficacy versus safety is ultimately a matter of clinical judgment and patient preference, we nevertheless caution against the indiscriminate use of dronedarone. To further understand how dronedarone will fare against amiodarone in the wider population with heart disease, more studies with longer follow-up are needed. At the very least, these studies need to demonstrate superior tolerability of dronedarone without unacceptable loss of efficacy in the maintenance of sinus rhythm and quality of life, or without an increase in morbidity or mortality compared with amiodarone. Until then, dronedarone may be best viewed only as half a step forward in our efforts to expand the antiarrhythmic armamentarium.

Torp-Pedersen and colleagues agree with Singh et al that dronedarone, like other antiarrhythmic drugs, has only moderate efficacy, but “whether it is more or less efficacious than flecainide, sotalol, and propafenone when rhythm control is pursued needs to be tested in randomized trials.” They further point out that the safety profile of other antiarrhythmics is even less well studied than dronedarone, suggesting the possibility that it is impossible to rule out very high risks with these drugs.

Torp-Pederson et al point out that rhythm control is the strategy often chosen by patients and physicians and conclude that dronedarone is an option for intermediate-risk patients and that for low-risk patients “dronedarone provides the only antiarrhythmic drug with a large safety database to prove reasonable safety. The safety knowledge of dronedarone may result in patient and physician preference of dronedarone as first-line therapy, with a possible switch to amiodarone when sinus rhythm is no longer maintained.”

Sanjay Kaul sent the following comment to CardioBrief in response to the editorial:

In general, the editorialist’s remarks regarding safety concerns with antiarrhythmic agents are on target. Safety is a key component in clinical decision-making process. Whether the potential for improved short-term tolerability of dronedarone versus its reduced efficacy compared to amiodarone is an acceptable tradeoff is ultimately a matter of clinical judgment and patient preference. However, I cannot envision dronedarone being recommended as a first-line therapy given its modest efficacy, lack of clear safety advantage, and huge cost disadvantage compared with amiodarone. I just don’t think it is prudent to use such a drug as first-line, especially when low-dose amiodarone (200 mg daily) is well-tolerated and has an acceptable safety track record. We agree with the NICE recommendations that on the basis of current evidence dronedarone’s use for the treatment of nonpermanent atrial fibrillation or atrial flutter can only be supported as a second- or third-line agent after guideline-recommended first-line agents have failed.

Editorial Comment: There’s another issue here that bothers me, relating to the partial paradox of deploying a low-efficacy drug for safety purposes in a low-risk population. AF patients are not static. Many of them will go on to progress to more advanced heart failure. And there is no good evidence to guide behavior in a patient with worsening heart failure who is already on dronedarone.

The larger problem here concerns drugs that are designed to be used only in low risk patients. Having failed in high risk heart failure patients in its earlier trials, Sanofi was able to cherry pick a lower-risk subgroup and gather the low-hanging fruit. In general, with the most successful drugs the risk-benefit equation means that higher risk patients are the ones most likely to benefit. There’s something very suspicious about a drug intended only for low risk patients.


Comments

  1. William Klein says

    My physician is a leading cardiologist in california, and a graduate of a great unversity—He’s quoted in journalseverywhere. . He put me on Mutaq some time ago, and I’m doing just fine. I’m sorry we live in an age of computers-stay off youor computer and trust your doctor, otherwise , find a new one–Don’t trust what you read-

    • Steve Linahan says

      I was put on Multaq as well be my cardiologist several months ago and doing well on it however I lowered my intake to 1 tablet a day instead of 2 and my success is still great. Why did I lower my dosage, that is because of the extreme cost of over $2400 for 180 day supply of Multaq which bumped me into the “Donut hole” on my Medicare insurance. I am also taking Eloquis which is also pricey about $400. This makes the drug costs unaffordable for many patients as out of pocket drug costs will cost you over $10k year. Alternatives are a real concern for patients which Dr Kaul clearly points out there are trade offs on effectiveness, side effects and cost. All three are valid parameters. Just because one works for you and you can afford to pay exorbitant drug prices does not preclude that the analysis is defective and to ignore the assessment as bogus internet postings. Trusting doctors blindly is not good advice for anyone ask them and they will advise you to research and educate yourself too. An informed patient makes a better patient. One should always know risks and side effects as most doctors do not tell you everything about their treatment plan and if you are uneducated and don’t ask the right questions or are surprise by effects…after the fact effect issues are a bad time to have that discussion. As with any situation the more you know your option the better prepared you are for being a partner in your health choices. Please be aware that doctors are human and they vary on their treatment plans as there is not one plan that works for all and even for each patient.

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