Compositions and methods for lowering triglycerides

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 stable statin therapy having fasting triglycerides of about 200 mg/dl to less than 500 mg/dl comprising administering to the subject about 2 g to about 4 g per day of a pharmaceutical composition comprising eicosapentaenoic acid and docosahexaenoic acid in free acid form for a period effective to reduce fasting triglycerides in the subject compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant eicosapentaenoic acid and docosahexaenoic acid for said period. 
     
     
         2 . The method of  claim 1  wherein the composition is administered to the subject 1 to 4 times per day. 
     
     
         3 . The method of  claim 2  wherein the composition is present in one or more capsules. 
     
     
         4 . The method of  claim 3  wherein 2 g of the composition is administered to the subject per day and each of said one or more capsules contains about 800 mg to about 1200 mg of eicosapentaenoic acid. 
     
     
         5 . The method of  claim 4  wherein each of said one or more capsules contains not more than about 10% by weight of any individual fatty acid selected from linolenic acid, alpha-linolenic acid, stearadonic acid, eicosatrienoic acid and docasapentaenoic acid. 
     
     
         6 . The method of  claim 3  wherein 4 g of the composition is administered to the subject per day and each of said one or more capsules contains about 2000 mg to about 2400 mg of eicosapentaenoic acid. 
     
     
         7 . The method of  claim 3  wherein about 3 g of the pharmaceutical composition is administered to the subject per and wherein the composition contains about 2000 mg to about 2400 mg eicosapentaenoic acid. 
     
     
         8 . The method of  claim 1  wherein the period effective to reduce fasting triglycerides is about 1 week to about 15 weeks. 
     
     
         9 . The method of  claim 8  wherein the period effective to reduce fasting triglycerides is about 1 week to about 12weeks. 
     
     
         10 . The method of  claim 9  wherein the period effective to reduce fasting triglycerides is about 1 week to about 5 weeks. 
     
     
         11 . The method of  claim 8  wherein the subject exhibits an increase in serum EPA and DHA at the end of said period effective to reduce fasting triglycerides. 
     
     
         12 . The method of  claim 1  wherein the subject has a baseline fasting LDL-C level of 40 mg/dl to 100 mg/dl and a fasting triglyceride level of 200 mg/dl to 500 mg/dl immediately prior to initial administration of the pharmaceutical composition. 
     
     
         13 . The method of  claim 12  wherein the subject has a baseline fasting non-HDL-C of 200 mg/dl to 300 mg/dl, a baseline fasting total cholesterol of 250 mg/dl to 300 mg/dl, a baseline fasting VLDL-C of 140 mg/dl to 200 mg/dl, and a baseline fasting HDL-C of 10 mg/dl to 80 mg/dl immediately prior to initial administration of the pharmaceutical composition. 
     
     
         14 . The method of  claim 13  wherein upon administering to the subject 2 g to about 4 g of said pharmaceutical composition daily for said period, the subject further exhibits (a) substantially no change or a reduction in fasting non-HDL-C compared to a fasting non-HDL-C level in a subject maintained on stable statin therapy without concomitant eicosapentaenoic acid or docosahexaenoic acid therapy for said period; and (b) substantially no change or a reduction in fasting VLDL-C compared to a fasting VLDL-C level in a subject maintained on stable statin therapy without concomitant eicosapentaenoic acid or docosahexaenoic acid therapy for said period. 
     
     
         15 . The method of  claim 13  wherein upon administering to the subject about 2 g to about 4 g of said pharmaceutical composition daily for said period the subject further exhibits: (a) a reduction in fasting triglycerides of at least about 25% compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant eicosapentaenoic acid or docosahexaenoic acid therapy for said period; and (b) a reduction in fasting non-HDL-C of at least about 5% compared to a fasting non-HDL-C level in a subject maintained on stable statin therapy without concomitant eicosapentaenoic acid or docosahexaenoic acid therapy for said period.