Role of New Drugs for Management of Atrial Fibrillation

James M Hollands PharmD BCPS; Mollie Gowan PharmD; Jennifer N Riney PharmD BCPS; Eli N Deal PharmD BCPS; Andrew M Kates MD


The Annals of Pharmacotherapy. 2012;46(12):1656-1670. 

In This Article

Abstract and Introduction


Objective: To evaluate the role of newer agents in the management of atrial fibrillation (AF).
Data sources: EMBASE and MEDLINE were searched (up to June 2012) combining medication names with atrial fibrillation, humans, clinical trials, and pharmacoeconomic. References of the articles identified and were also reviewed.
Study selection and data extraction: Studies were limited to the English language with clinical or pharmacoeconomic end points followed by the consensus of 3 authors.
Data synthesis: Formulated to reduce some of the adverse effects associated with amiodarone by removing the iodine component, dronedarone has improved clinical outcomes over placebo when used in paroxysmal or persistent AF; however, it is less efficacious than amiodarone. Worse outcomes with dronedarone have been seen in patients with heart failure or permanent AF. It has not been compared to antiarrhythmic agents other than amiodarone, and pharmacoeconomic evaluations are lacking. Dabigatran 150 mg is superior to warfarin in preventing stroke or systemic embolism and has been associated with lower rates of vascular-associated mortality. Although the rates of major bleeding were not significantly different between the 2 agents, gastrointestinal bleeding and myocardial infarction occurred more frequently with dabigatran. Dabigatran appears to have the most pharmacoeconomic benefit over warfarin in patients with a higher risk of stroke. Rivaroxaban is noninferior to warfarin for the prevention of stroke and systemic embolism, with no difference in the rates of major bleeding. Cost-effectiveness studies have not been performed with this agent at this time. In patients with AF who were not suitable candidates for warfarin, apixaban is superior to aspirin in preventing stroke or systemic embolism without increasing the risk for major bleeding. Additionally, apixaban is superior to warfarin in preventing stroke or systemic embolism, results in fewer bleeding events, and is associated with lower mortality. Apixaban is not cost-effective against aspirin when used for a short duration but gains superiority with prolonged use or in patients with higher risks of stroke. Additionally, apixaban appears to offer a pharmacoeconomic advantage over warfarin at no to minimal cost. Each new anticoagulant lacks a reversal agent and an assay to detect the presence of the anticoagulant, as well as long-term data when used in the clinical setting.
Conclusions: Use of dronedarone should be limited to patients with paroxysmal or persistent AF and should not be used in patients with heart failure or with permanent AF. Newer antithrombotic agents appear to be promising alternatives for the prevention of stroke in patients with AF; however, more data are needed to understand their role.


A trial fibrillation (AF) is the most common clinically significant arrhythmia in the US. AF has been associated with an increased risk of stroke, heart failure (HF), and death.[1] Because of its significant morbidity and economic burden, AF has garnered much attention, even within Congress, which introduced House Resolution 295 that focused on "promoting awareness, diagnosis, and treatment of atrial fibrillation."[2] Pharmacologic management of AF can involve modulating the ventricular response, converting from AF to normal sinus rhythm (NSR), maintaining NSR, and providing stroke and systemic embolism prophylaxis. Significant limitations to current treatments provide ample opportunities for newer agents to establish a role in therapy. This review focuses on newer medications that either have recently received Food and Drug Administration (FDA) approval or were likely to be seeking approval soon (dronedarone, dabigatran, rivaroxaban, and apixaban).