Relative effects of different non-vitamin K antagonist oral anticoagulants on global thrombotic status in atrial fibrillation.
Non-vitamin K antagonist oral anticoagulants (NOACs) reduce the risk of thromboembolism in patients with atrial fibrillation (AF). There has been no head-to-head comparison of the effect of these agents on ex vivo thrombotic and thrombolytic status. Enhanced platelet reactivity and impaired endogenous thrombolysis are risk factors for recurrent thrombotic events. We aimed to assess the comparative effect of NOACs and warfarin using an ex vivo test of thrombosis and thrombolysis. Eighty patients with newly diagnosed non-valvular AF were tested before, and after being established on apixaban (n = 20), dabigatran (n = 20), rivaroxaban (n = 20), or warfarin (n = 20). Thrombotic status was assessed with the automated, point-of-care Global Thrombosis Test (GTT) that assesses both platelet reactivity and endogenous thrombolysis from native blood. The time taken to form an occlusive thrombus (occlusion time, OT) and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured. All anticoagulants caused OT prolongation compared to baseline (apixaban 403 ± 102s vs. 496 ± 125s, p = 0.006; dabigatran 471 ± 106s vs. 656 ± 165s, p < 0.00001; rivaroxaban 381 ± 119s vs. 579 ± 158, p < 0.00001; warfarin 420 ± 145s vs. 604 ± 124s, p < 0.00001). Apixaban reduced LT from baseline (1895[1702-2167]s vs. 1435[347-1990]s; p = 0.006). A trend for LT reduction was seen with other NOACs (dabigatran 1594[1226-2069]s vs. 1539[561-2316]s, p = 0.499; rivaroxaban 2085[1366-2428]s vs. 1885[724-2420]s, p = 0.295) but not with warfarin (1490[1206-1960]s vs. 1776[1545-2334], p = 0.601). Our results suggest that NOACs and warfarin have a similar favorable effect on reducing platelet reactivity. All NOACs exhibited a trend toward enhancing endogenous thrombolytic status, although this was significant only for apixaban. This raises the possibility of using NOACs to enhance impaired endogenous fibrinolysis in patients at high-thrombotic risk.
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.|b Postgraduate Medical School , University of Hertfordshire , Hertfordshire , UK.
Mohamed
M
Farag
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.|c National Heart & Lung Institute, Imperial College , London , UK.
Maria
M
Niespialowska-Steuden
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.
Osita
O
Okafor
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.
Benjamin
B
Artman
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.
Manivannan
M
Srinivasan
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.
Arif
A
Khan
b Postgraduate Medical School , University of Hertfordshire , Hertfordshire , UK.
Keith
K
Sullivan
b Postgraduate Medical School , University of Hertfordshire , Hertfordshire , UK.
David
D
Wellsted
a Department of Cardiology , East and North Hertfordshire NHS Trust , Hertfordshire , UK.|b Postgraduate Medical School , University of Hertfordshire , Hertfordshire , UK.|c National Heart & Lung Institute, Imperial College , London , UK.
Diana A
DA
Gorog
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D001780:Blood Coagulation Tests; D015897:Comorbidity; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010979:Platelet Function Tests; D012307:Risk Factors; D013923:Thromboembolism / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
D000925:Anticoagulants
Anticoagulant drugs; atrial fibrillation; fibrinolysis; platelet function tests; thromboembolism