Novel Antithrombotic Drugs on the Horizon
The Ultimate Promise to Prevent Clotting While Avoiding Bleeding
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Diseases associated with arterial thrombosis or venous thrombosis are leading causes of mortality and morbidity globally. Since the 1930s, antithrombotic therapy has been the cornerstone of medical therapy for thrombotic diseases. However, the success of antithrombotic therapy has come at the cost of one of the most dreaded iatrogenic complications—bleeding. Recently, new evidence has emerged on potentially important differences between thrombosis and hemostasis, thereby raising the possibility of developing new antithrombotic drugs that do not cause bleeding.
Scope of Antithrombotic-Associated Bleeding
All currently used antithrombotic drugs in the clinic are associated with an inherent risk of bleeding. For example, the risk of serious major bleeding with a non–vitamin K antagonist oral anticoagulant is ≈2% to 3%, with the risk of intracranial hemorrhage of ≈0.3 to 0.5% per annum.1 Likewise nonmajor bleeding with aspirin approximates 2%, and the rates of major and life-threatening bleeding rises significantly in those over 75 years of age to >2% per year.2 Thus, a significant proportion of patients at high risk of thrombotic disease are vulnerable to bleeding complications and often miss out on potentially beneficial antithrombotic therapy. Importantly, aside from the mortality and morbidity directly linked to the index bleeding event, there is a large body of evidence demonstrating that hemorrhagic complications are associated with adverse clinical outcomes.3 Despite the introduction of new anticoagulants, such as the non–vitamin K antagonist oral anticoagulants and newer antiplatelet drugs, we have reached a tipping point with regard to the achievable balance between antithrombotic potency and bleeding risk with current antithrombotic approaches. Therefore, there remains an unmet clinical need for new antithrombotic approaches that maintain efficacy while preserving hemostasis.
New Insights Into Thrombosis and Hemostasis
Recently, major progress has been achieved in our understanding of the factors that may differentially regulate pathological thrombosis from hemostasis based on the introduction of intravital microscopy, …