Diseases related to thrombosis are a major cause of morbidity and mortality. This year, an estimated 1.26 million Americans will have a new or recurrent myocardial infarction. In addition, ≈2.3 to 3.2 million people are currently affected with atrial fibrillation in the United States, with up to a 7% risk of embolic stroke leading to ≈100 000 strokes per year. Importantly, thrombus formation is responsible for the majority of acute coronary syndromes and embolic strokes, as well as diseases due to venous thrombosis. The importance of the identification of novel ways to regulate thrombosis, particularly ones that are readily adaptable as therapeutic targets, has contributed to the development of new drugs to prevent arterial thrombosis in the clinical settings of unstable coronary syndromes, stent thrombosis, peripheral arterial occlusion, and thrombotic stroke.
As the number of patients with thrombotic diseases grows, there has been continued interest in the development and appropriate use of antithrombotic and platelet inhibitor therapies. Thus, as our understanding of hemostasis and thrombosis continues to evolve, so does the development of agents directed toward treating relevant cardiovascular and thromboembolic diseases. This development continues to be fueled by scientific discovery, the growing number of patients and indications for antithrombotics, and unmet medical needs with currently available therapies. Novel groups of therapeutics are being developed while existing therapies are being further studied for expanding indications, enhanced combinations, and safety profile. There has been continued development of coagulation inhibitors, with new formulations being developed. Oral thrombin inhibitors have progressed with both successes and failures. Targets for antiplatelet drugs continue to be defined, leading to novel therapies as well as the development of additional agents in already successful classes. The use of genetics and individually guided dosing with anticoagulants and antithrombotics holds the promise of fewer side effects and complications, particularly with bleeding.
The goal of this series is to highlight the rapid development and ongoing evolution that have defined new treatments in hemostatic and thrombotic pathways and uncovered their therapeutic relevance. There have been significant advances in the development of platelet inhibitors. In the area of ADP receptor antagonists, there is the development of agents with rapid onset and shorter half-lives or drugs that are reversible and would allow for urgent surgical procedures. New direct and reversible P2Y12 antagonists might be attractive alternatives to existing thienopyridines. Also, during the last decade, there has been growing development of therapies that target platelet adhesion and activation. The hope is that these specific targets will allow for separation of platelet inhibition from bleeding.
In addition, this series will highlight the utility and limitations of nutritional supplements and vitamins and their role in platelet thrombosis. It will also highlight potential side effects of supplements, most notably bleeding. The importance of new anticoagulants and combination antithrombotic therapies will be examined. In a related topic, the emerging role of bleeding as a major factor in limiting the benefit of therapies will be considered. A central goal in the use of these therapies is the development of useful tools to guide treatment that will maintain vascular patency while minimizing bleeding complications. The hope is that this update will both highlight the many new antithrombotic drugs that are being intensively studied as well as highlight the tight link between treating thrombosis and bleeding. In summary, the diseases that lead to thrombotic occlusions are a major source of morbidity and mortality, and enormous strides have been made during the past decade in the development and use of antithrombotic and platelet inhibitor therapies.