The Use Of Oral Ranolazine To Convert New Or Paroxysmal Atrial Fibrillation: A Review Of Experience With Implications For Possible "Pill In The Pocket" Approach To Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. High dose oral anti-arrhythmics may cardiovert some paroxysmal AF. This "pill in pocket" approach has allowed patients to treat themselves on an as needed basis. Pro-arrhythmic concerns have limited the usefulness of this approach to patients without structural heart disease. Ranolazine is an anti-anginal agent, which inhibits abnormal late Na+ channel currents in cardiomyocytes and decreases sodium-calcium overload. Ranolazine is a potent inhibitor of after-depolarizations, which have been implicated in the initiation and propagation of AF. Because ranolazine has no known pro-arrhythmic effects, it could be useful as a safe "pill in the pocket" agent if it were effective in converting AF. We describe our experience using oral ranolazine to convert new or paroxysmal AF. Method: 2000 mg of ranolazine were administered to 18 patients with new (11 patients) or paroxysmal (7 patients) AF of at least 3, but not greater than 48 hours duration. Most patients (14) were in the hospital at the time ranolazine was administered. Age, sex, echocardiographic data, associated health conditions and structural heart disease were recorded. Successful conversion was defined as restoring sinus rhythm within 6 hours of ranolazine administration. Results: All but 1 patient had some form of structural heart disease and all but 2 patients had left atrial enlargement. Thirteen of 18 patients converted to sinus rhythm. No pro-arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived intolerance (other than constipation) were noted. The 72% conversion rate was comparable to other reported "pill in the pocket" protocols. Conclusion: High dose oral ranolazine shows utility as a possible safe agent to convert new or paroxysmal AF. Lack of blinded controls and small numbers limits the power of this observation

The effect of ranolazine on maintaining sinus rhythm in patients with resistant atrial fibrillation

Background: Atrial fibrillation (AF) may arise out of anomalous impulse activity at atrial venous junctions. Triggered activity may be a source of abnormal impulse activity. Ranolazine is an anti-anginal agent, which inhibits normal and abnormal late Na+ channel current in the ventricle and peak Na+ channel current in the atrium. This produces an energy sparing effect and stabilizes cardiac membranes. Ranolazine is a potent inhibitor of triggered activity. The purpose of this report is to describe our initial experience with ranolazine used in patients with resistant AF.Methods: Seven patients (4 males, 3 females, 67 ± 9 years) who developed recurrent AF within hours to a few days of restoring sinus rhythm despite AF ablation and /or failing one or more anti-arrhythmic agents were started on ranolazine (500-1000 mg/twice/day) after stopping all other anti-arrhythmic therapy. All but one patient had some form of associated structural heart disease. Results: Two patients received no apparent benefit from ranolazine developing recurrent AF within 2 days. All other patients derived significant benefit. Four patients have experienced no recurrent AF. The other patient relapsed at 3 months and again at 6 months. The mean time in sinus rhythm to date, or to the first relapse, for the five responders was 27 ± 11 weeks. No clinically evident pro-arrhythmic episodes occurred. Conclusion: Ranolazine was helpful in maintaining sinus rhythm in the majority of patients in which more established measures had failed. A controlled prospective trial is warranted to further investigate the efficacy of ranolazine in AF