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Anti-Arrhythmic..

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Atrial fibrillation (AF) is considered the most common arrhythmia in practice and is associated with an increased risk of stroke and mortality.1 In individuals with persistent AF with symptoms, the current recommendation for management is cardioversion, which can be either electrical or pharmacological.1,2 However, many patients will experience relapse following cardioversion due to remodeling of the heart.1 Studies have suggested that the heart can overcome remodeling after 2-4 weeks of stable normal sinus rhythm (NSR). While cardioversion works well to convert AF into NSR, there is a high-risk of recurrence during the weeks following cardioversion.1 Anti-arrhythmic therapy can help sustain NSR after cardioversion, and a major question is whether short-term anti-arrhythmic therapy would suffice to prevent further episodes of atrial fibrillation compared to long-term therapy.3

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Kirchhof and colleagues conducted the Flecainide Short-Long trial (Flec-SL), a prospective, randomized, open-label, blinded endpoint trial, to compare short-term versus long-term antiarrhythmic therapy for the prevention of AF recurrence. Criteria for inclusion were documented persistent atrial fibrillation, planned cardioversion, therapeutic oral anticoagulation for at least three weeks prior to enrollment or a negative trans-esophageal echocardiography, and 18 years of age or older. Patients were excluded if the received antiarrhythmic therapy other than flecainide prior to enrollment (unless stopped 5 half lives prior to enrollment), amiodarone within the past six months, or had a contraindication to flecainide. Patients received flecainide 48 hours or more prior to electrical cardioversion. Then, patients were randomized to one of three arms following cardioversion: placebo, flecainide (200-300 mg daily) treatment for 4 weeks, or flecainide treatment for 6 months. The primary outcome was time to persistent atrial fibrillation or death. Once superiority of flecainide versus placebo was shown, the placebo arm was ended.3,4

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The study enrolled 635 patients with a mean age of 63.7 years and duration of AF of 27.5 months. Only 6% of the patients had coronary artery disease. Recurrent persistent AF was more common with short-term treatment (46%) versus long-term treatment (39%, p=0.2081). No deaths occurred during the trial. The difference between the two groups in patients who did not have persistent AF did not reach the criteria for non-inferiority. In a post-hoc analysis of patients who did not reach the primary endpoint in the first month, long-term treatment was found to be superior to short term treatment in preventing persistent AF or death. Serious adverse effects were not common in either group. There was no difference in quality of life between the groups.3

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The study found that long-term treatment (defined as 6 months in this study) was the preferred duration to prevent AF recurrence. The study also found that flecainide was effective in preventing recurrence after cardioversion.3 There was a low number of patients with structural heart disease or heart failure since flecainide should not be used in these types of patients, therefore extrapolation of the results is limited in terms of the optimal duration of therapy to other patient populations....

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