Compositions and methods for lowering triglycerides without raising ldl-c levels in a subject on concomitant statin therapy

Abstract

In various embodiments, the present invention provides compositions and methods for treating and/or preventing cardiovascular-related diseases in subject in need thereof.

1 . A method of lowering triglycerides in a subject on statin therapy having fasting triglycerides of about 200 mg/dl to less than 500 mg/dl comprising, administering to the subject on statin therapy from about 2 g to about 4 g per day of a pharmaceutical composition comprising at least 96% pure ethyl-EPA for a period effective to lower fasting triglycerides in the subject compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         2 . The method of  claim 1  wherein the subject has serum LDL-C levels of about 40 mg/dl to about 115 mg/dl at a baseline prior to administration of the composition. 
     
     
         3 . The method of  claim 1  wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting Lp-PLA2 compared to a fasting Lp-PLA2 level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         4 . The method of  claim 1  wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting VLDL-C compared to a fasting VLDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         5 . The method of  claim 1 , wherein upon administering the composition to the subject daily for said period, the subject exhibits at least a 5% reduction in fasting triglycerides compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         6 . The method of  claim 5 , wherein upon administering the composition to the subject daily for said period, the subject exhibits at least a 10% reduction in fasting triglycerides compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         7 . The method of  claim 6 , wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting LDL-C compared to a fasting LDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         8 . The method of  claim 1 , wherein the subject consumes a Western diet. 
     
     
         9 . The method of  claim 1 , wherein the subject is on stable statin therapy for at least 4 weeks immediately prior initial administration of the composition. 
     
     
         10 . The method of  claim 1 , wherein the subject is at LDL goal at time of said initial administration of the composition. 
     
     
         11 . The method of  claim 1 , wherein the subject has a fasting LDL-C level of at least 40 mg/dl and less than 100 mg/dl and a fasting triglyceride level of at least 200 mg/dl and less than 500 mg/dl immediately prior to initial administration of the composition. 
     
     
         12 . A method of lowering triglycerides in a subject on statin therapy having fasting triglycerides of about 200 mg/dl to less than 500 mg/dl and fasting a LDL-C level of about 40 mg/dl to about 100 mg/dl comprising, administering to the subject 2 g to about 4 g per day of a pharmaceutical composition comprising at least 96% pure ethyl-EPA for a period effective to lower triglycerides in the subject. 
     
     
         13 . The method of  claim 12  wherein upon administering the composition to the subject for said period, the subject exhibits a reduction in fasting non-LDL compared to a fasting non-LDL level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         14 . The method of  claim 12  wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits a reduction in fasting VLDL-C compared to a fasting VLDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         15 . The method of  claim 12  wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting apolipoprotein B compared to a fasting apolipoprotein B level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         16 . The method of  claim 12  wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting total cholesterol compared to a fasting total cholesterol level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 
     
     
         17 . A method of lowering triglycerides in a subject on statin therapy having fasting triglycerides of about 200 mg/dl to less than 500 mg/dl comprising, administering to the subject on statin therapy from 2 g to 4 g per day of a pharmaceutical composition comprising at least 96% pure ethyl-EPA thereby to lower fasting triglycerides in the subject by least 5% compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period, and wherein administration of the composition does not result in a statistically significant increase in fasting LDL-C compared to a fasting LDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period.