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 - 23 . (canceled) 
     
     
         24 . 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. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 24 , wherein the increase decrease in ω-3/ω-6 in plasma and/or RBCs is at least 60%. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 24 , wherein the increase includes an increase in ω-3/ω-6 in plasma of at least 60%. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 24 , wherein the increase includes an increase in ω-3/ω-6 in RBCs of at least 60%. 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 24 , wherein the omega-3 fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid and docosahecaenoic acid. 
     
     
         35 . The method of  claim 24 , 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, adrenic acid, and ω-6 docosapentaenoic acid. 
     
     
         36 . The method of  claim 24 , wherein the subject is administered about 2 g/day of EPA. 
     
     
         37 . The method of  claim 24 , wherein the subject is administered about 4 g/day of EPA. 
     
     
         38 . The method of  claim 24 , 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. 
     
     
         39 . 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. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 39 , wherein the increase is at least about 60%. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 39 , wherein the increase includes an increase in the ratio in plasma of at least 60%. 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 39 , wherein the increase includes an increase in the ratio in RBCs of at least 50%. 
     
     
         47 . (canceled) 
     
     
         48 . The method of  claim 39 , wherein the omega-3 fatty acids include one or more of: α-linolenic acid, stearidonic acid, eicosatrienoic acid, ω-3 arachidonic acid, eicosapentaenoic acid, ω-3 docosapentaenoic acid and docosahecaenoic acid. 
     
     
         49 . The method of  claim 39 , 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. 
     
     
         50 . The method of  claim 39 , wherein the subject is administered about 2 g/day of EPA. 
     
     
         51 . The method of  claim 39 , wherein the subject is administered about 4 g/day of EPA. 
     
     
         52 . The method of  claim 39 , 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. 
     
     
         53 . 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 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. 
     
     
         54 . (canceled) 
     
     
         55 . The method of  claim 53 , wherein the decrease is at least about 7%. 
     
     
         56 . (canceled) 
     
     
         57 . (canceled) 
     
     
         58 . The method of  claim 53 , wherein the decrease includes a decrease in the ratio in plasma of at least 4%. 
     
     
         59 . (canceled) 
     
     
         60 . The method of  claim 53 , wherein the decrease includes a decrease in the ratio in RBCs of at least 11%. 
     
     
         61 . (canceled) 
     
     
         62 . The method of  claim 53 , 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, adrenic acid, and ω-6 docosapentaenoic acid. 
     
     
         63 . The method of  claim 53 , 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. 
     
     
         64 . The method of  claim 53 , wherein the subject is administered about 2 g/day of EPA. 
     
     
         65 . The method of  claim 53 , wherein the subject is administered about 4 g/day of EPA. 
     
     
         66 . The method of  claim 53 , 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. 
     
     
         67 - 87 . (canceled)