Methods of Preventing Cardiovascular Events in Residual Risk Dyslipidemic Populations

Abstract

The present invention provides pharmacological interventions for the treatment of dyslipidemia, and to the reduction of residual risk of cardiovascular disease and adverse cardiovascular events in patients on intense statin use or with well-controlled LDL-C concentrations. In particular, the invention relates to the use of pemafibrate to prevent cardiovascular events in populations at-risk due to risk factors such as type 2 diabetes mellitus with dyslipidemia in spite of intense statin use or well-controlled LDL-C.

1 - 65 ) (canceled) 
     
     
         66 ) A method of reducing the risk of an adverse cardiovascular event in a patient with type 2 diabetes mellitus comprising administering to the patient a therapeutically effective amount of pemafibrate therapy, wherein:
 a) prior to commencing the pemafibrate therapy:
 i) the patient has an LDL-C concentration ≤70 mg/dL; or 
 ii) the patient is on a stable dose of moderate to high intensity statin therapy; 
   b) the patient has an HDL-C concentration ≤40 mg/dL prior to commencing the pemafibrate therapy;   c) the patient has a fasting TG concentration ≥200 mg/dL and <500 mg/dL prior to commencing the pemafibrate therapy;   d) the patient continues the statin therapy after commencing the pemafibrate therapy; and   e) the therapeutically effective amount of pemafibrate or pharmaceutically acceptable salt thereof is from 0.2 to 1.0 mg, administered orally per day.   
     
     
         67 ) The method of  claim 66 , wherein the patient does not have atherosclerosis and does not have cardiovascular disease. 
     
     
         68 ) The method of  claim 66 , wherein the patient is on a stable dose of high intensity statin therapy prior to commencing the pemafibrate therapy. 
     
     
         69 ) The method of  claim 66 , wherein the patient has an LDL-C concentration ≤70 mg/dL prior to commencing the pemafibrate therapy. 
     
     
         70 ) The method of  claim 66 , wherein the patient has atherosclerosis. 
     
     
         71 ) The method of  claim 66 , wherein the method reduces the risk of a cardiovascular event without decreasing LDL-C concentrations. 
     
     
         72 ) The method of  claim 66 , wherein the patient is at risk for rhabdomyolysis as shown by elevated creatinine kinase. 
     
     
         73 ) The method of  claim 66 , wherein the patient has renal insufficiency. 
     
     
         74 ) The method of  claim 66 , wherein the patient has renal failure. 
     
     
         75 ) A method of treating a patient having one or more risk factors and an LDL-C concentration ≤70 mg/dL to reduce the risk of an adverse cardiovascular event, comprising administering to the patient a therapeutically effective amount of pemafibrate or a pharmaceutically acceptable salt thereof, wherein the therapeutically effective amount of pemafibrate or pharmaceutically acceptable salt thereof is from 0.2 to 1.0 mg, administered orally per day. 
     
     
         76 ) The method of  claim 75 , wherein the patient has type 2 diabetes mellitus. 
     
     
         77 ) The method of  claim 75 , wherein the patient has a fasting TG concentration ≥200 mg/dL and <500 mg/dL. 
     
     
         78 ) The method of  claim 75 , wherein the patient has an HDL-C concentration ≤40 mg/dL. 
     
     
         79 ) The method of  claim 75 , wherein the patient has:
 a) type 2 diabetes mellitus;   b) a fasting TG concentration ≥200 mg/dL and <500 mg/dL; and   c) an HDL-C concentration ≤40 mg/dL.   
     
     
         80 ) A method of treating a patient on a stable dose of moderate to high intensity statin therapy and having one or more cardiovascular risk factors to reduce the risk of an adverse cardiovascular event, comprising administering to the patient a therapeutically effective amount of pemafibrate or a pharmaceutically acceptable salt thereof, wherein the therapeutically effective amount of pemafibrate or pharmaceutically acceptable salt thereof is from 0.2 to 1.0 mg, administered orally per day, wherein the patient is on a stable dose of moderate to high intensity statin therapy prior to commencing the pemafibrate administration. 
     
     
         81 ) The method of  claim 80 , wherein the patient has an LDL-C concentration ≤70 mg/dL. 
     
     
         82 ) The method of  claim 80 , wherein the patient has type 2 diabetes mellitus. 
     
     
         83 ) The method of  claim 80 , wherein the patient has a fasting TG concentration ≥200 mg/dL and <500 mg/dL. 
     
     
         84 ) The method of  claim 80 , wherein the patient has an HDL-C concentration ≤40 mg/dL. 
     
     
         85 ) The method of  claim 80 , wherein the patient has:
 a) type 2 diabetes mellitus;   b) a fasting TG concentration ≥200 mg/dL and <500 mg/dL; and   c) an HDL-C concentration ≤40 mg/dL.