COST-EFFECTIVENESS OF DRONEDARONE COMPARED TO AMIODARONE FOR PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION

Purpose:  Dronedarone was FDA-approved in 2009 for the treatment of paroxysmal or persistent atrial fibrillation or atrial flutter in patients who are in sinus rhythm or who will be cardioverted.  Dronedarone is more costly than its structural analogue, amiodarone, and preliminary data show it to be less effective than amiodarone but associated with fewer adverse events.  Therefore, the purpose of this analysis was to compare the cost-effectiveness of dronedarone to amiodarone. 

Methods:  A Markov model was used to estimate the costs and effectiveness of dronedarone and amiodarone in patients with paroxysmal atrial fibrillation. Costs were measured in 2009 US dollars, and effectiveness was measured in quality-adjusted life years (QALYs). All costs and probabilities were drawn from published literature, and medication costs were expressed as average wholesale prices.  A five-year time horizon and three-month cycle length were used.  Costs and effectiveness were discounted at 3% per year.  The base case analysis assumed a 10% probability of significant hyperthyroidism, hypothyroidism, and pulmonary toxicity in patients receiving amiodarone, and a relative risk of 0.5 for dronedarone versus amiodarone for each adverse event. A probabilistic sensitivity analysis was used to determine the probability of cost-effectiveness when all model variables were sampled from distributions reflecting uncertainty.

Results:  In the base case analysis, the dronedarone strategy is dominated, costing $6690 more and having  0.07 fewer QALYs than the amiodarone strategy.  In one-way sensitivity analyses, pulmonary toxicity risk is the only variable that could alter this conclusion. If the ten-year probability of amiodarone-related pulmonary toxicity is ≥32% (clinically plausible range: 2%-17%), dronedarone is not dominated; if this probability is 52% or 44% then the ICER for dronedarone is $50,000 or $100,000/QALY, respectively. At an acceptability threshold of $100,000/QALY, amiodarone is favored if its pulmonary toxicity risk is ≤36% even if there is no risk of dronedarone pulmonary toxicity.  A probabilistic sensitivity analysis favors amiodarone in >98% of 5000 iterations at a $100,000/QALY threshold.

Conclusions:  Dronedarone is more costly and less effective than amiodarone if the five-year probability of pulmonary toxicity with amiodarone is less than 32%. Due to its higher cost, we did not find dronedarone to be economically reasonable unless it has no pulmonary risk and amiodarone-related pulmonary toxicity occurs more frequently than previously reported.