Abstract 16181: Ranolazine Reduces the Late Recurrences of Atrial Fibrillation. An Exploratory Analysis of the Raffaello Study

Introduction: Ranolazine (RAN) is an antianginal drug that inhibits late sodium currents and reduces atrial excitability, thus being potentially effective in atrial fibrillation (AF). The phase 2 study RAFFAELLO tested 3 ranolazine doses (375mg, 500mg, 750mg BID) vs. placebo in maintaining sinus rhythm after successful cardioversion (CV) in patients with persistent AF. A trend was found toward reduced AF recurrence in the two higher doses although the study missed the primary endpoint to show superiority of any dose over placebo, The RAN 375 dose was ineffective. Hypothesis: This exploratory analysis compared the combined RAN 500 + 750 mg group with the combined placebo + RAN 375 mg group to gain insights into the time course of the antifibrillatory effects of RAN. Methods: Patients with persistent AF were randomized 2 h after CV to the study treatment lasting 16 weeks. Primary endpoint was the median time from randomisation to first AF recurrence. The RAN 500 and 750 mg patients were pooled and compared with pooled RAN 375 and placebo patients. Effect on early ( 14 days) AF recurrence was assessed. Results: The population comprised 238 patients (placebo+RAN 375:n=120, RAN 500+750:n=118).The figure shows the recurrence-free survival curves of the 2-group analysis (p=0.02). Early AF recurrences were moderately and non significantly reduced by high RAN doses (relative risk 0.78, 95%CI 0.53-1.13, p=0.16) whereas late recurrences were significantly reduced by 50% (relative risk 0.51, 95%CI 0.25-1.00, p=0.03). Conclusions: The 500+750 mg RAN doses reduced the recurrence of AF compared with placebo + the ineffective 375 mg dose. The data suggest that ranolazine may be less effective early after CV when inflammation and atrial remodelling are present and more effective against late AF recurrences, when triggers are likely to play a dominant role. Late sodium current blockers, by reducing the triggers may represent a novel approach against atrial fibrillation. ![][1] [1]: /embed/graphic-1.gif