Inhibiting thrombosis without causing bleeding: Can EP3 blockers fulfil the dream?

摘要

Pharmacologists designing and clinicians dealing with antithrombotic drugs have always faced the problem that preventing thrombosis-by inhibiting one or more ofthe haemostatic pathways-always entails increased risk of bleeding. This paradigm has been over and over confirmed with the newer antithrombotic drugs, either inhibiting platelet function-such as prasu-grel, ticagrelor, or cangrelor-or inhibiting coagulation-the new direct oral anticoagulants, such as thrombin or activated Factor X inhibitors.2 No matter which new drug has been tested compared with older drugs or placebo, here the issue at stake is never increased potency or better safety in isolation, but always a better benefit-risk balance. Contrary to, for example, drugs lowering low-density lipoprotein (LDL) cholesterol, antithrombotic treatments have always been a perilous navigation between the Scylla of thrombosis and the Charybdis of bleeding. This latter itself also conjures with thrombosis because ofthe ominous consequences of bleeding, itself often precipitating thrombosis for a variety of reasons. Therefore, always protection from thrombosis has come to the expenses of increased bleeding-no free lunch.