Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

FDA Drug Safety Communication – Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events

The FDA (Food and Drug Administration) has sent out a safety announcement about dronedarone (Multaq).

The U.S. Food and Drug Administration (FDA) is reviewing data from a clinical trial that was evaluating the effects of the antiarrhythmic drug Multaq (dronedarone) in patients with permanent atrial fibrillation. The study was stopped early after the data monitoring committee found a two-fold increase in death, as well as two-fold increases in stroke and hospitalization for heart failure in patients receiving Multaq compared to patients taking a placebo.[1]

It will be interesting to see how many patients are included in the data. Is this just a statistical aberration or is this evidence of an unrecognized adverse effect of dronedarone?

Currently Multaq is approved for use in a different, but related patient population (see Facts about Multaq box). The approval of Multaq was based on another trial (ATHENA) in which use of Multaq was associated with a decreased number of deaths compared to placebo.1[1]

A bit of irony in the names of the studies. In Greek mythology, Pallas was killed by Athena. Here, PALLAS[2] appears to be invalidating the results of ATHENA.[3]

What does this mean for EMS and for patients who have been taking dronedarone?

Punt.

Dronedarone is for A Fib (Atrial Fibrillation). This is for patients who are not always in A Fib. Dronedarone may work by altering the rhythm, by altering the rate, by some other mechanism, or by some combination of these. Dronedarone is an antiarrhythmic that works in all of the antiarrhythmic categories.

Call a doctor. For patients, they should contact their doctor to see what is recommended. The doctor may not be able to provide much information, since the results are still being analyzed, but the doctor can write a prescription for something else and recommend the best way to transition from one medication to another.

241,000 patients at an extra 1/2 of 1 percent death rate over 2 years equals about 1% = 2,410 extra deaths?

What happens without dronedarone?

More time in A Fib, or a faster heart rate, or something else, or some combination of these.

What happens with dronedarone?

That is the big question. The table below provides the preliminary data.

When the analysis is done we will know more, but we will still have a lot of unknowns.

Footnotes:

[1] FDA Drug Safety Communication: Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events
7/21/2011
FDA
Safety Announcement

[2] Permanent Atrial fibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS)
ClinicalTrials.gov
Last Updated 7/11/2011
Ongoing Trial Information

[3] Effect of dronedarone on cardiovascular events in atrial fibrillation.
Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, Connolly SJ; ATHENA Investigators.
N Engl J Med. 2009 Feb 12;360(7):668-78. Erratum in: N Engl J Med. 2009 Jun 4;360(23):2487. N Engl J Med. 2011 Apr 14;364(15):1481.
PMID: 19213680 [PubMed – indexed for MEDLINE]

Free Full Text from N Engl J Med with link to Free Full Text PDF Download

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