Methods for treating atrial fibrillation

Abstract

The subject invention provides methods for reducing stroke rate, methods for preventing atrial remodeling, and methods for reversing atrial remodeling by administering budiodarone to reduce atrial fibrillation (AF) episode duration and an anticoagulant (AC). According to some methods of the invention, the average AF episode duration can be reduced to less than about 24, 5, 3 or 1 hour(s), and the maximum AF episode duration may be reduced to less than about 20, 10 or 5 hours. According to some methods of the invention, the reduced stroke rate upon administration of budiodarone and AC is less than the age-adjusted overall stroke rate. Further, some methods provide that patients who were refractory to one or more anti-arrhythmic drugs prior to administration of budiodarone may also be treated. Some methods provide for prevention of atrial remodeling and others provide for the reversal of atrial remodeling, including methods to quantify the reversal of atrial remodeling. In some methods of the invention, budiodarone is administered 400 mg BID or more preferably 600 mg BID.

1 . A method for treating a refractory atrial fibrillation patient comprising administering to patient refractory to one or more anti-arrhythmic drugs an amount of budiodarone effective to reduce atrial fibrillation burden (AFB). 
     
     
         2 . The method of  claim 1 , further comprising administration of an effective amount of anticoagulant (AC) selected from the group consisting of AZD0837, dabigatran etexilate, dabigatran, ximelagatran, melagatran, argatroban, apixaban, rivaroxaban, YM466, betrixaban, edoxaban, otamixaban, tecarfarin and warfarin. 
     
     
         3 . The method of  claim 1 , wherein average atrial fibrillation episode duration is reduced. 
     
     
         4 . The method of  claim 1 , wherein said patient is identified as at risk for stroke. 
     
     
         5 . The method of  claim 4 , wherein said patient has a CHADS 2  (Cardiac failure, Hypertension, Age, Diabetes, Stroke/transient ischemic event [doubled]) score of 1 or more. 
     
     
         6 . The method of  claim 1 , wherein said atrial fibrillation is paroxysmal atrial fibrillation (PAF). 
     
     
         7 . The method of  claim 1 , wherein said atrial fibrillation is persistent atrial fibrillation. 
     
     
         8 . The method of  claim 1 , wherein average atrial fibrillation episode duration is greater than about 5 hours prior to administration of budiodarone. 
     
     
         9 . The method of  claim 1 , wherein average atrial fibrillation episode duration is reduced to less than about 5 hours. 
     
     
         10 . The method of  claim 1 , wherein average atrial fibrillation episode duration is reduced to less than about 3 hours. 
     
     
         11 . The method of  claim 1 , wherein average atrial fibrillation episode duration is reduced to less than about 1 hour. 
     
     
         12 . The method of  claim 2 , wherein average atrial fibrillation episode duration is decreased by more than 50% after treatment. 
     
     
         13 . The method of  claim 2 , wherein average atrial fibrillation episode duration is decreased by more than 70% after treatment. 
     
     
         14 . The method of  claim 1 , wherein AFB is decreased by at least 70% after treatment. 
     
     
         15 . The method of  claim 1 , wherein the amount of budiodarone is 400 mg BID. 
     
     
         16 . The method of  claim 1 , wherein the amount of budiodarone is 600 mg BID. 
     
     
         17 . The method of  claim 2 , wherein said anticoagulant is warfarin. 
     
     
         18 . The method of  claim 2 , wherein said anticoagulant is tecarfarin. 
     
     
         19 . The method of  claim 1 , wherein mean duration of normal sinus rhythm (NSR) between episodes of atrial fibrillation is increased. 
     
     
         20 . The method of  claim 1 , wherein said one or more anti-arrhythmic drugs is a class III anti-arrhythmic drug. 
     
     
         21 . The method of  claim 19 , wherein said one or more class III anti-arrhythmic drug is dofetilide or ibutilide. 
     
     
         22 . The method of  claim 1 , wherein said one or more anti-arrhythmic drugs is amiodarone. 
     
     
         23 . The method of  claim 1 , wherein said one or more anti-arrhythmic drugs is a class I anti-arrhythmic drug. 
     
     
         24 . The method of  claim 9 , wherein said one or more class I anti-arrhythmic drug is flecanide or quinidine.