Synergy between low molecular weight heparin and platelet aggregation inhibitors, providing a combination therapy for the prevention and treatment of various thromboembolic disorders

Abstract

This invention is directed to a combination therapy comprising the administration of a low molecular weight heparin such as tinzaparin and a platelet GPIIb/IIIa antagonist such as roxifiban for treating, preventing and reducing the risk of thromboembolic disorders.

What is claimed is:  
     
         1 . A method for treating a condition selected from the group: acute coronary ischemic syndrome, thrombosis, thromboembolism, thrombic occlusion and reclusion, restenosis, transient ischemic attack, and first or subsequent thrombotic stroke comprising administration of a sub-therapeutic dose of a low molecular weight heparin and a sub-therapeutic dose of a platelet GPIIb/IIIa antagonist to a mammal in need of such treatment.  
     
     
         2 . A method according to  claim 1 , wherein the platelet GPIIb/IIIa antagonist is roxifiban.  
     
     
         3 . A method according to  claim 1 , wherein the low molecular weight heparin is tinzaparin.  
     
     
         4 . A method according to  claim 1 , wherein the administration is subcutaneous.  
     
     
         5 . A pharmaceutical composition comprising a platelet GPIIb/IIIa antagonist and a low molecular weight heparin and a pharmaceutically acceptable carrier.  
     
     
         6 . A pharmaceutical composition according to  claim 5 , wherein the platelet GPIIb/IIIa antagonist is roxifiban.  
     
     
         7 . A pharmaceutical composition according to  claim 5 , wherein the low molecular weight heparin is tinzaparin.  
     
     
         8 . A kit comprising a platelet GPIIb/IIIa antagonist and a low molecular weight heparin for subcutaneous injection.  
     
     
         9 . A method of treating thrombosis in a mammal comprising administering to said mammal a combination of: (i) a subtherapeutic dose of GPIIb/IIIa antagonist selected from the group consisting of abciximab, eptifibatide, tirofiban, lamifiban, lefradafiban, sibrafiban, orbofiban, xemilofiban, a compound of the formula (A):  
       
         
           
           
               
               
           
         
       
       and a compound of the formula (B):  
       
         
           
           
               
               
           
         
       
       and (ii) aspirin or (iii) a low molecular weight heparin selected from the group consisting of tinzaparin, certoparin, parnaparin, nadroparin, ardeparin, enoxaparin, reviparin, reviparin and dalteparin.  
     
     
         10 . The method of  claim 9  wherein the combination of (i) and (ii) or (iii) provides a synergistic effect.  
     
     
         11 . The method of  claim 9 , wherein the combination administered is a combination of the GPIIb/IIIa antagonist and a low molecular weight heparin.  
     
     
         12 . The method of  claim 11 , wherein the GPIIb/IIIa antagonist is administered in a subtherapeutic amount.  
     
     
         13 . The method of  claim 11 , wherein the GPIIb/IIIa antagonist is compound A or compound B.  
     
     
         14 . The method of  claim 11 , wherein the low molecular weight heparin is dalteparin (fragmin).  
     
     
         15 . The method of  claim 11 , wherein the GPIIb/IIIa antagonist is compound A or compound B and the low molecular weight heparin is dalteparin (fragmin).  
     
     
         16 . The use of a combination of: (i) a subtherapeutic dose of GPIIb/IIIa antagonist selected from the group consisting of abciximab, eptifibatide, tirofiban, lamifiban, lefradafiban, sibrafiban, orbofiban, xemilofiban, a compound of the formula (A):  
       
         
           
           
               
               
           
         
       
       and a compound of the formula (B):  
       
         
           
           
               
               
           
         
       
       and (ii) aspirin or (iii) a low molecular weight heparin selected from the group consisting of tinzaparin, certoparin, parnaparin, nadroparin, ardeparin, enoxaparin, reviparin, fragmin and dalteparin for the manufacture of a medicament for the treatment of thrombosis.  
     
     
         17 . A method of treating thrombosis in a mammal comprising administering to said mammal (i) tissue plasminogen activator and (ii) a compound of the formula: