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.

What is claimed is: 
     
         1 . A method of lowering triglycerides and high sensitivity C-reactive protein (“hsCRP”) in a subject on statin therapy having baseline fasting triglycerides of about 200 mg/dl to less than 500 mg/dl and a baseline fasting Apolipoprotein B (“Apo B”) level of about 217 mg/dl or about 227 mg/dl, the method comprising determining a baseline fasting triglyceride level, a baseline fasting Apo B level, and a baseline hsCRP level associated with the subject; and thereafter administering to the subject about 2 grams or about 4 grams per day of ethyl eicosapentaenoate. 
     
     
         2 . The method of  claim 1  further comprising determining a baseline fasting low-density lipoprotein cholesterol (“LDL-C”) level associated with the subject before the administering, wherein an LDL-C level associated with the subject after the administering is not increased compared to the baseline fasting LDL-C level. 
     
     
         3 . The method of  claim 1 , wherein the subject is administered about 2 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 10% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         4 . The method of  claim 2 , wherein the subject is administered about 2 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 10% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         5 . The method of  claim 1 , wherein the subject is administered about 4 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 21% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         6 . The method of  claim 2 , wherein the subject is administered about 4 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 21% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         7 . The method of  claim 1  wherein after the administering an Apo B level associated with the subject is lower than the baseline fasting Apo B level compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         8 . The method of  claim 1  further comprising determining a baseline fasting very low-density lipoprotein cholesterol (“VLDL-C”) level associated with the subject, wherein after the administering an VLDL-C level associated with the subject is lower than the baseline fasting VLDL-C level compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         9 . The method of  claim 1  further comprising determining a baseline fasting lipoprotein associated phospholipase A2 (“LP-PLA 2 ”) level associated with the subject, wherein after the administering an LP-PLA 2  level associated with the subject is lower than the baseline fasting LP-PLA 2  level compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         10 . The method of  claim 1  further comprising determining baseline fasting levels of LDL-C, Apo B, VLDL-C and Lp-PLA 2  associated with the subject, wherein after the administering levels of LDL-C, Apo B, VLDL-C and Lp-PLA 2  associated with the subject are lower than the baseline fasting levels compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate. 
     
     
         11 . The method of  claim 10 , wherein the subject receives about 2 grams of ethyl eicosapentaenoate per day. 
     
     
         12 . The method of  claim 10 , wherein the subject receives about 4 grams of ethyl eicosapentaenoate per day. 
     
     
         13 . The method of  claim 2 , wherein the subject has a baseline fasting LDL-C level of about 82 mg/dl. 
     
     
         14 . The method of  claim 8 , wherein the subject has a baseline fasting VLDL-C level of about 225 mg/dl or about 233 mg/dl. 
     
     
         15 . The method of  claim 9 , wherein the subject has a baseline fasting Lp-PLA 2  level of about 217 mg/dl or about 224 mg/dl. 
     
     
         16 . The method of  claim 10 , wherein the subject has:
 a baseline fasting LDL-C level of about 82 mg/dl;   a baseline fasting Apo B level of about 217 mg/dl or about 227 mg/dl;   a baseline fasting VLDL-C level of about 225 mg/dl or about 233 mg/dl; and   a baseline fasting Lp-PLA 2  level of about 217 mg/dl or about 224 mg/dl.   
     
     
         17 . The method of  claim 1 , wherein the subject is administered about 4 grams per day of ethyl eicosapentaenoate, and wherein a hsCRP level associated with the subject after the administering is lower than the baseline hsCRP level compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.