This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of dronedarone for the treatment of atrial fibrillation (AF) or atrial flutter based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The population considered in the submission were adult clinically stable patients with a recent history of or current non-permanent AF. Comparators were the current available anti-arrhythmic drugs: class 1c agents (flecainide and propafenone), sotalol and amiodarone. Outcomes were AF recurrence, all-cause mortality, stroke, treatment discontinuations (due to any cause or due to adverse events) and serious adverse events. The main evidence came from four phase III randomised controlled trials, direct and indirect meta-analyses from a systematic review, and a synthesis of the direct and indirect evidence using a mixed-treatment comparison. Overall, the results from the different synthesis approaches showed that the odds of AF recurrence appeared statistically significantly lower with dronedarone and other anti-arrhythmic drugs than with non-active control, and that the odds of AF recurrence are statistically significantly higher for dronedarone than for amiodarone. However, the results for outcomes of all-cause mortality, stroke and treatment discontinuations and serious adverse events were all uncertain. A discrete event simulation model was used to evaluate dronedarone versus antiarrhythmic drugs and standard therapy alone. The incremental cost-effectiveness ratio of dronedarone was relatively robust and less than 20,000 pound per quality-adjusted life-year. Exploratory work undertaken by the ERG identified that the main drivers of cost-effectiveness were the benefits assigned to dronedarone for all-cause mortality and stroke. Dronedarone is not cost-effective relative to its comparators when the only effect of treatment is a reduction in AF recurrences. In conclusion, uncertainties remain in the clinical effectiveness and cost-effectiveness of dronedarone. In particular, the clinical evidence for the major drivers of cost-effectiveness (all-cause mortality and stroke), and consequently the additional benefits attributed in the economic model to dronedarone compared to other antiarrhythmic drugs are highly uncertain. The final guidance, issued by NICE on 25 August 2010, states that: Dronedarone is recommended as an option for the treatment of non-permanent atrial fibrillation only in people: whose atrial fibrillation is not controlled by first-line therapy (usually including beta-blockers), that is, as a second-line treatment option, and who have at least one of the following cardiovascular risk factors: - hypertension requiring drugs of at least two different classes, diabetes mellitus, previous transient ischaemic attack, stroke or systemic embolism, left atrial diameter of 50 mm or greater, left ventricular ejection fraction less than 40% (noting that the summary of product characteristics [SPC] does not recommend dronedarone for people with left ventricular ejection fraction less than 35% because of limited experience of using it in this group) or age 70 years or older, and who do not have unstable New York Heart Association (NYHA) class III or IV heart failure.
Furthermore, 'People who do not meet the criteria above who are currently receiving dronedarone should have the option to continue treatment until they and their clinicians consider it appropriate to sop'.