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 increasing a ratio of omega-3 fatty acids to omega-6 fatty acids (ω-3/ω-6) in plasma or RBCs of a subject having baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl and on stable statin therapy, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits an increase in ω-3/ω-6 in plasma and/or RBCs of at least 50% compared to a control subject on stable statin therapy without EPA, wherein the control subject also has baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl. 
     
     
         2 . The method of  claim 1 , wherein the increase in ω-3/ω-6 in plasma and/or RBCs is at least 60%. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the omega-3 fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid and docosahecaenoic acid. 
     
     
         6 . The method of  claim 1 , wherein the omega-6 fatty acids include one or more of: linoleic acid, 7-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, and adrenic acid. 
     
     
         7 . The method of  claim 1 , wherein the subject is administered about 2 g/day of EPA. 
     
     
         8 . The method of  claim 1 , wherein the subject is administered about 4 g/day of EPA. 
     
     
         9 . The method of  claim 1 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject. 
     
     
         10 . A method of increasing a ratio of omega-3 fatty acids to total fatty acids in plasma or RBCs of a subject having baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl and on stable statin therapy, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits an increase in the ratio of omega-3 fatty acids to total fatty acids in plasma and/or RBCs of at least 50% compared to a control subject on stable statin therapy without EPA, wherein the control subject also has baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl. 
     
     
         11 . The method of  claim 10 , wherein the increase is at least about 60%. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The method of  claim 10 , wherein the omega-3 fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid and docosahecaenoic acid. 
     
     
         15 . The method of  claim 10 , wherein the total fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid, docosahecaenoic acid, linoleic acid, 7-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, adrenic acid, ω-6 docosapentaenoic acid, myristoleic acid, palmitoleic acid, cis-vaccenic acid, oleic acid, gondoic/gadoleic acid, erucic acid, nervonic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid and lignoceric acid. 
     
     
         16 . The method of  claim 10 , wherein the subject is administered about 2 g/day of EPA. 
     
     
         17 . The method of  claim 10 , wherein the subject is administered about 4 g/day of EPA. 
     
     
         18 . The method of  claim 10 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject. 
     
     
         19 . A method of decreasing a ratio of omega-6 fatty acids to total fatty acids in plasma or RBCs of a subject having baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl and on stable statin therapy, the method comprising:
 determining a baseline ratio of omega-6 fatty acids to total fatty acids in the subject; and   thereafter administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of EPA per day, wherein upon administering the composition to the subject daily for a period of 12 weeks, the subject exhibits a decrease in the ratio of omega-6 fatty acids to total fatty acids in plasma and/or RBCs of at least 4% compared to a control subject on stable statin therapy without EPA, wherein the control subject also has baseline fasting triglycerides of about 200 mg/dl to about 500 mg/dl.   
     
     
         20 . The method of  claim 19 , wherein the decrease is at least about 7%. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . The method of  claim 19 , wherein the omega-6 fatty acids include one or more of: linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, and adrenic acid. 
     
     
         24 . The method of  claim 19 , wherein the total fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid, docosahecaenoic acid, linoleic acid, γ-linolenic acid, eicosadienoic acid, dihomo-γ-linolenic acid, ω-6 arachidonic acid, adrenic acid, ω-6 docosapentaenoic acid, myristoleic acid, palmitoleic acid, cis-vaccenic acid, oleic acid, gondoic/gadoleic acid, erucic acid, nervonic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid and lignoceric acid. 
     
     
         25 . The method of  claim 19 , wherein the subject is administered about 2 g/day of EPA. 
     
     
         26 . The method of  claim 19 , wherein the subject is administered about 4 g/day of EPA. 
     
     
         27 . The method of  claim 19 , wherein the subject further exhibits no increase, no substantial increase, or a reduction in plasma and/or RBC levels of DHA compared to the control subject.