scholarly journals Assessing Safety of Direct Thrombin Inhibitors, Direct Factor Xa Inhibitors and Vitamin K Antagonists in Patients with Atrial Fibrillation: A Nation-Wide Propensity Score Matched Cohort from Sweden

2020 ◽  
Vol Volume 12 ◽  
pp. 1029-1038
Author(s):  
Marie Linder ◽  
Anastasia Nyman Iliadou ◽  
Helle Kieler ◽  
Bengt Danielsson ◽  
Natalia Borg ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Propensity Score ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Matched Cohort ◽  
Direct Factor ◽  
Direct Factor Xa Inhibitors

Effects of Dabigatran, a Direct Thrombin Inhibitor, as Compared to the Direct Factor Xa Inhibitors, Rivaroxaban and Apixaban, on Tissue Factor-Induced Human Platelet Aggregation in Platelet Rich Plasma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1884-1884 ◽  
Author(s):  
Joanne van Ryn ◽  
Monika Kink-Eiband ◽  
Norbert Hauel ◽  
Henning Priepke ◽  
Wolfgang Wienen
Keyword(s):  
Platelet Aggregation ◽  
Tissue Factor ◽  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Direct Factor ◽  
Direct Factor Xa Inhibitors

Abstract Direct thrombin inhibitors (DTIs) have been shown to be very potent inhibitors of platelet function when platelets are activated with thrombin. This action does not occur by direct binding of the DTI to the platelet PAR-1/-4 receptor, but indirectly, by reducing thrombin concentrations and thereby reducing the interactions of thrombin with its receptor on the platelet. It was hypothesized that both thrombin and factor Xa inhibitors could inhibit platelet aggregation, if the stimulus to initiate aggregation was higher in the cascade than factor Xa, such as tissue factor. Thus, dabigatran, a DTI, and the direct factor Xa inhibitors, rivaroxaban and apixaban were tested. Free flowing whole blood (60 ml) was obtained from an antecubital vein using an 18 gauge needle from healthy human volunteers. Blood was collected in tubes containing 3.13% sodium citrate (1 in 10 dilution with whole blood). Blood was centrifuged at 200x g to obtain platelet rich plasma (PRP). Samples (300 μL PRP) were placed in a 6-channel aggregometer, equilibrated for 5 min at 37°C and calibrated with PPP from same individual (0–1 Volts). Photometric tracings were continuously digitally recorded over 5 min following the addition of tissue factor and curves were evaluated as AUC over this time interval. Each PRP sample was incubated with 2 mg/ml Pefabloc®FG (Gly-Pro-Arg-Pro) to prevent fibrin polymerisation, 5 mM CaCl2 and increasing concentrations of dabigatran or factor Xa inhibitor. Tissue factor stimulus (range, 5–27 μl of 10 ml Innovin solution) was tailored for each individual, so that the minimum concentration that resulted in maximum aggregation was used. As positive controls, aggregation was also performed after stimulating with ADP (10 μM), collagen (2 μg/ml), TRAP (20 μM) or ecarin (0.1 U/ml). All substances inhibited tissue factor-induced platelet aggregation in a concentration-dependent manner. Dabigatran was the most potent inhibitor of platelet aggregation among the substances tested, with an IC50 of 35 nM, rivaroxaban and then apixaban followed, with IC50s of 312 and 817 nM, respectively. All substances had no effect on platelet aggregation induced by ADP, collagen and TRAP. Dabigatran was a potent inhibitor of ecarin-induced platelet aggregation, while the factor Xa inhibitors had no effect, as expected from their mechanism of action. Thus, these studies demonstrate that both direct thrombin inhibitors (by inhibiting thrombin) and direct factor Xa inhibitors (by preventing thrombin generation) indirectly inhibit platelet aggregation, though dabigatran was more potent than rivaroxaban and apixaban under these experimental conditions. Thus, these substances may not only be effective in venous/stasis thrombotic episodes where fibrin formation plays an important role, but may also be effective in more platelet dominant, arterial thrombosis settings.

scholarly journals A REVIEW ON A COMPARATIVE STUDY ON EFFECTIVENESS AND SAFETY OF NOVEL ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION

2019 ◽  
Vol 7 (2) ◽  
Author(s):  
Priyanka P K ◽  
Mathew George ◽  
Lincy Joseph
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Therapeutic Option ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Systemic Embolism ◽  
Anticoagulant Drugs

Atrial fibrillation (AF) is characterized as an extremely rapid and disorganized atrial activation. These irregular heartbeats will cause blood to collect within the heart and potentially form a clot, which can travel to a person’s brain and cause a stroke. AF increases stroke risk by 3 to 5 fold. Vitamin K antagonists (VKAs) are highly effective for the prevention of stroke, mainly of ischemic origin, in patients with AF. For this reason, VKAs are currently recommended in all AF patients at moderate to high risk for stroke or systemic embolism (SSE). VKAs have significant limitations, particularly their unpredictable anticoagulant response and numerous food and drug interactions, mandating regular laboratory monitoring. These limitations make treatment with VKAs problematic for many patients; as a result, only about half of all potentially eligible AF patients are treated with VKAs. Over the last several years, novel oral anticoagulant drugs (NOACs), including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban & rivaroxaban), have been developed. New orally administered anticoagulant drugs have emerged as potential alternatives to VKAs for the prevention of ischaemic stroke or systemic embolism in patients with chronic atrial fibrillation. Novel oral anticoagulants (NOACs), due to their a lot of predictable therapeutic result and more favorable haemorrhagic risk profile, represent a particularly attractive therapeutic option in AF patients. Keywords:  Novel oral anticoagulants (NOACs), Vitamin K antagonist (VKAs), Atrial fibrillation, Apixaban, Dabigatran, Rivaroxaban.

scholarly journals Atrial Fibrillation: A Review of Recent Studies with a Focus on Those from the Duke Clinical Research Institute

Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Meena P. Rao ◽  
Sean D. Pokorney ◽  
Christopher B. Granger
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
The United States ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Number Of Patients ◽  
Worse Prognosis ◽  
Research Institute

Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute.

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