Updates on Pharmacologic Management of Atrial Fibrillation

NEW ORLEANS, LA—At ACC.11, the American College of Cardiology's 60th Annual Scientific Session, leading cardiologists discussed the changing landscape of atrial fibrillation (AF) management due to the availability and development of novel antiarrhythmic agents and new evidence supporting the use of anti-inflammatory drugs.

Current and Emerging Antiarrhythmic Drug Therapy

New antiarrhythmic agents include dronedarone, FDA-approved for the management of AF and atrial flutter (AFL), and investigational agents such as vernakalant. Dronedarone, an amiodarone-like compound, lacks the iodine component of amiodarone and thus is associated with reduced toxicity. Gerald V. Naccarelli, MD presented data from the ATHENA trial, which evaluated the efficacy of dronedarone in 4,628 patients with paroxysmal or persistent AF against placebo.

ATHENA study results demonstrated a 24% risk reduction (P<0.001) of the cumulative incidence of cardiovascular hospitalization or death and a 26% reduction (P<0.001) in risk of first cardiovascular hospitalization. Additionally, fewer patients developed permanent AF on dronedarone therapy. The PALLAS study will further assess this effect. Amiodarone was shown in the DIONYSOS trial to be more effective than dronedarone. An increased rate of adverse events, however, reduces the clinical benefit of amiodarone.

Vernakalant, approved in the E.U. in 2010 for the rapid conversion of recent onset AF to sinus rhythmn in adults (non-surgery patients with AF of ≤7 days and for post-cardiac surgery patients with AF of ≤3 days), is being evaluated in the U.S. as an “atrial specific” antiarrhythmic for atrial efficacy without ventricular proarrhythmia. The intravenous formulation of vernakalant was recommended by the Cardio-Renal Advisory Committee to the FDA based on two pivotal trials in recent onset AF, which revealed 52% conversion compared with 4% with placebo at a mean time of 8–11 minutes. An orally available formulation of vernakalant is being investigated for the prevention of AF.

James Reiffel, MD reported results from several small pilot studies evaluating the off-label use of ranolazine for new onset paroxysmal AF, AF that has become refractory to previously effective agents and post-ablation, and for AF termination in patients who have become refractory to previously effective class IC agents. Data showed that 24 of 31 patients converted to normal sinus rhythm within 6 hours and demonstrated no apparent proarrhythmic or adverse hemodynamic events.

AntiInflammatory Drug Therapy in the Management of AF

Atrial fibrillation after cardiac surgery is associated with elevation of inflammation markers, particularly in AF associated with atrial remodeling, cardiovascular disease, heart failure, obesity, hypertension, and older age. Inflammation plays a smaller role in recurrent, persistent, or permanent AF in which fibrosis has already been established.

Mina Chung, MD presented data supporting the use of “upstream” therapies, including ACE inhibitors and ARBs in patients with underlying structural heart disease and heart failure/LV dysfunction or hypertension. A meta-analysis of several large randomized clinical trials demonstrated a 48% risk reduction of AF with ACE inhibitors and ARBs therapy. Statin therapy may also be considered in patients with structural heart diseases or heart failure, said Dr. Chung. However, these therapies were less effective in patients without structural heart disease and are not recommended for primary prevention of AF in patients. A meta-analysis of steroids in the prevention of post-operative AF in cardiac surgery patients demonstrated a 44% reduction in relative risk. Steroids and statins are effective in preventing AF after cardiac surgery.