Dronedarone guidelines may be short on evidence

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Clinical practice guidelines involving dronedarone, a drug used to control arrhythmias in patients with atrial fibrillation, may not be based on the best available evidence, a special communication published online Feb. 17 in JAMA Internal Medicine found.

Investigators led by Primiano Iannone, MD, of Tigullio Hospital in Lavagna, Italy, evaluated three guidelines on the dronedarone (Multaq, Sanofi-Aventis) made by medical societies. The researchers used the Grading of Recommendations Assessment, Development and Evaluation (GRADE), which can measure the relevance of outcomes, the quality of evidence and patients’ preferences.

They compared dronedarone recommendations to conclusions they made using GRADE. Their GRADE analysis included the same seven studies used to make the clinical practice guidelines.

They considered mortality, cardioembolic events and serious adverse reactions as the three main outcomes and scored the overall quality of evidence as the lowest quality score for these outcomes for whatever outcomes information was available. Overall, their reassessment of the guidelines considered favorable and unfavorable outcomes, patient preferences and medication cost.

When used for rhythm control, dronedarone was associated with 13 excess deaths per 1,000 patients compared with placebo. The drug was also less effective than amiodarone (Cordarone, Wyeth-Ayerst) for atrial fibrillation recurrences (294 vs. 214). There were more serious adverse events requiring discontinuation of the drug compared with amiodarone.

Despite these findings, all of the guidelines recommended dronedarone to prevent recurrences of atrial fibrillation and two recommended it to control heart rate.

“Using the GRADE method and the primary study data considered in these guidelines, we concluded that any recommendation in favor of dronedarone for either rhythm or rate control of atrial fibrillation was not justified,” the authors wrote.

While they acknowledged that their findings may be limited in scope, they argued that there are “many recent examples of clinical practice guidelines from medical specialty societies in which panel members have substantial financial conflicts of interest and in which the methods are problematic.”