Thrombosis

Thrombosis / 2013 / Article / Tab 1

Review Article

New Oral Anticoagulants in the Treatment of Pulmonary Embolism: Efficacy, Bleeding Risk, and Monitoring

Table 1

Comparison of the pharmacokinetic and pharmacodynamic features of oral anticoagulant therapies [15, 18, 21, 2331].

CharacteristicWarfarinApixabanDabigatranRivaroxaban

Mechanism of actionVKORC1 enzyme inhibitorDirect Factor Xa inhibitor
Direct Factor IIa (Thrombin) inhibitorDirect Factor Xa inhibitor

ProdrugNoNoYesNo

Approved indicationsVTE prevention
VTE treatment
Atrial fibrillation
Valvular heart disease
(all approved in EMA, HC, FDA)
VTE prevention
(EMA, HC)
Nonvalvular AF
(EMA, HC, FDA)
VTE prevention
(EMA, HC)
Nonvalvular AF
(EMA, HC, FDA)
VTE prevention
(EMA, HC, FDA)
Nonvalvular AF
(EMA, HC, FDA)
VTE treatment
(EMA, HC, FDA)

FDA black box warningsAgent can cause major or fatal bleeding; Regular INR monitoring is necessary; drugs, dietary changes, and other factors affect INR levels (FDA)Discontinuation in patients without adequate continuous anticoagulation increases the risk of stroke (FDA)None to dateDiscontinuing places patients at an increased risk of thrombotic events; Risk of spinal/epidural hematoma during neuraxial anesthesia/spinal puncture (FDA)

DosingVariable, patient specificFixed, twice daily
With dose reduction in two of the following patients: (per FDA)
(1) Age ≥ 80 years
(2) Weight ≤ 60 kg
(3) Serum creatinine ≥1.5 mg/dL
Fixed, twice daily
With dose reduction in patients with renal dysfunction (per FDA)
VTE prevention and nonvalvular AF:
Fixed, once daily
With dose reduction in patients with renal dysfunction (per FDA)
VTE treatment:
Fixed, twice daily 3 weeks then fixed, once daily
Not to be used if ClCr <30 mL/min

(h)41–31–32–4

Half-life (h)20–60 1212–175–9

Bioavailability (F)100%50%6%
(~75% if capsule opened)
10 mg: 80–100%
(regardless of food)
20 mg: 66% (without food).
Food increases absorption#

Renal Clearance >90% as inactive metabolites25%80%*36% unchanged drug*  
33% as inactive metabolites
Mostly via secretion not glomerular filtration

CYP metabolism+>90%
(S-enantiomer is a substrate for 2C9 and 2C19 while R-enantiomer is a substrate for 1A1, 1A2, and 3A4 )
15%
(primary substrate for CYP3A4; minor contributions by others, without active metabolites)
No30%
(substrate for CYP3A4, CYP2J2)

P-glycoprotein (P-gp)+NoYesYesYes

Dietary considerationsDietary vitamin KNoneNoneVTE prevention dose: does not specify
AFIB: Take with evening meal
VTE treatment: Take with food

Influence on routine coagulation assay
 Protime (PT)

 aPTT No/

 Thrombin time (TT) NoNo No

 Coagulation assay
 used to monitor efficacy
INR (Protime) NoneNoneNone

 Clinically validated
 Reversal agent
Vitamin K, FFP, PCC, Factor VIIa, aPCCNoneNoneNone

EMA: European Medicines Agency; HC: Health Canada; FDA: U.S. Food and Drug Administration
AF: Atrial Fibrillation; CYP: cytochrome P450; VKORC1: C1 subunit of the vitamin K epoxide reductase enzyme; FFP: Fresh Frozen Plasma; PCC: Prothrombin Complex Concentrate.
Does not bind to antithrombin.
#Rivaroxaban 15 mg tablet, if available, should be taken with food.
*Dose adjustment for level of renal dysfunction required.
+Potential source for drug-drug interactions—review full package insert for details.

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