New anticoagulants: Moving beyond the direct oral anticoagulants

2020 ◽  
Vol 19 (1) ◽  
pp. 20-29
Author(s):  
James C. Fredenburgh ◽  
Jeffrey I. Weitz
2016 ◽  
Vol 157 (38) ◽  
pp. 1507-1510
Author(s):  
Róbert Gábor Kiss

Antithrombotic drug therapy is a main cornerstone – sometimes a fairly uneven cornerstone – of today’s clinical practice. Patients treated with antithrombotic drugs appear sometimes unawaited at those of our colleagues, who are not necessarily experts of this narrow field. Furthermore, new and newer molecules of antiplatelet and anticoagulant medicines have come into practice, frequently in combination. This dramatic development has been important to patients; pharmacological – and recently nonpharmacological – antithrombotic treatment has paved the way to improve current modalities in cardiology. Combining elements of the “old four” (heparin, coumadin, aspirin, clopidogrel) have been the basis of any improvement for a long time. Nowadays, there has been an involvement of new drugs, direct oral anticoagulants into practice. It is time now to catch up in using new anticoagulants, regardless of our current speciality in medicine. Orv. Hetil., 2016, 157(38), 1507–1510.


Blood ◽  
2017 ◽  
Vol 129 (2) ◽  
pp. 147-154 ◽  
Author(s):  
James C. Fredenburgh ◽  
Peter L. Gross ◽  
Jeffrey I. Weitz

Abstract Despite the introduction of direct oral anticoagulants (DOACs), the search for more effective and safer antithrombotic strategies continues. Better understanding of the pathogenesis of thrombosis has fostered 2 new approaches to achieving this goal. First, evidence that thrombin may be as important as platelets to thrombosis at sites of arterial injury and that platelets contribute to venous thrombosis has prompted trials comparing anticoagulants with aspirin for secondary prevention in arterial thrombosis and aspirin with anticoagulants for primary and secondary prevention of venous thrombosis. These studies will help identify novel treatment strategies. Second, emerging data that naturally occurring polyphosphates activate the contact system and that this system is critical for thrombus stabilization and growth have identified factor XII (FXII) and FXI as targets for new anticoagulants that may be even safer than the DOACs. Studies are needed to determine whether FXI or FXII is the better target and to compare the efficacy and safety of these new strategies with current standards of care for the prevention or treatment of thrombosis. Focusing on these advances, this article outlines how treatment strategies for thrombosis are evolving and describes the rationale and approaches to targeting FXII and FXI. These emerging anticoagulant strategies should address unmet needs and reduce the systemic underuse of anticoagulation because of the fear of bleeding.


Blood ◽  
2020 ◽  
Vol 135 (5) ◽  
pp. 351-359 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Noel C. Chan

Abstract Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cause of vascular death after heart attack and stroke. Anticoagulation therapy is the cornerstone of VTE treatment. Despite such therapy, up to 50% of patients with DVT develop postthrombotic syndrome, and up to 4% of patients with PE develop chronic thromboembolic pulmonary hypertension. Therefore, better therapies are needed. Although direct oral anticoagulants are more convenient and safer than warfarin for VTE treatment, bleeding remains the major side effect, particularly in cancer patients. Factor XII and factor XI have emerged as targets for new anticoagulants that may be safer. To reduce the complications of VTE, attenuation of thrombin activatable fibrinolysis inhibitor activity is under investigation in PE patients to enhance endogenous fibrinolysis, whereas blockade of leukocyte interaction with the vessel wall is being studied to reduce the inflammation that contributes to postthrombotic syndrome in DVT patients. Focusing on these novel antithrombotic strategies, this article explains why safer anticoagulants are needed, provides the rationale for factor XII and XI as targets for such agents, reviews the data on the factor XII– and factor XI–directed anticoagulants under development, describes novel therapies to enhance fibrinolysis and decrease inflammation in PE and DVT patients, respectively, and offers insights into the opportunities for these novel VTE therapies.


2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Gabriello Marchetti ◽  
Francesco Bernardini ◽  
Michele Romoli ◽  
Stefano Urbinati

Sign in / Sign up

Export Citation Format

Share Document