Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding.
Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B2and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB2value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB2was -6.5% with warfarin (p=0.197), -29% with apixaban (p<0.001) and -31% with rivaroxaban (p<0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB2(B: -0.469, p<0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p<0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB2in the NOACs group (Rs: 0.527, p<0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p<0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2excretion compared to warfarin, suggesting that NOACs possess antiplatelet property.
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy. Electronic address: pasquale.pignatelli@uniroma1.it.
Pasquale
P
Pignatelli
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Daniele
D
Pastori
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Simona
S
Bartimoccia
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Danilo
D
Menichelli
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Tommasa
T
Vicario
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Cristina
C
Nocella
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Roberto
R
Carnevale
IClinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
Francesco
F
Violi
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003430:Cross-Sectional Studies; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D012307:Risk Factors; D000069552:Rivaroxaban / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011720:Pyrazoles; D011728:Pyridones; C098341:platelet membrane glycoprotein VI; C522181:apixaban; D013929:Thromboxane B2; D014859:Warfarin; C049235:11-dehydro-thromboxane B2; D000069552:Rivaroxaban
Anti Xa non-vitamin k oral anticoagulant; Atrial fibrillation; Glycoprotein VI; Platelet inhibitor; Thromboxane; Warfarin