Review Article

Antithrombotic Medication for Cardioembolic Stroke Prevention

Table 5

Comparison of anticoagulants. APPC: activated prothrombin complex concentrate; CYP3A4: cytochrome P450 enzyme 3A4; FFP: fresh frozen plasma; HIT: heparin-induced thrombocytopenia; Iv: intravenous; IU: international units; LMWH: low-molecular-weight heparins; PCC: prothrombin complex concentrate; P-gp: P-glycoprotein; rFVIIa: recombinant activated factor VII; Sc: subcutaneous; UFH: unfractioned heparins; *all should be used with caution with other anticoagulants, nonsteroid anti-inflammatory drugs, thrombolytics, or platelet inhibitors because of an increased risk of bleeding. ** Time to reach peak plasma concentrations and half-life elimination may be delayed after surgery; from [196204].

ParameterDabigatranRivaroxabanLMWHUFHWarfarin
EnoxaparinDalteparin

Routine coagulation monitoring requiredNoNo NoAl inicioYes
Use with renal insufficiencyModerate: dosage adjustment (150 mg daily)Moderate: use caution Moderate: use cautionModerate: yesModerate: use caution
Severe: contraindicatedSevere: not recommended Severe: dosage adjustmentSevere: use cautionSevere: use caution
Use with hepatic insufficiencyNot recommendedContraindicated Use cautionUse cautionUse caution
Potential for HITNoNo LowHighNo
Drug interactions*Quinidine, amiodarone, antacids, potent P-gp inhibitors (e.g., verapamil, clarithromycin)Potent inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, rifampicin). Strong CYP3A4 inducers (e.g., phenytoin, carbamazepine) No clinically significant
drug interactions known
No clinically significant drug interactions knownMultiple drugs
Reversal of anticoagulant effectrFVIIa, APCC (in rats) [35]rFVIIa, APCC (in rats and primates) [36, 37] Protamine sulfate (partial)Protamine sulfateVitamin K, FFP, PPC
TargetFactor Iia (thrombin) directFactor Xa direct Factor Xa and IIa (thrombin) indirectAntithrombin IIIVitamin K epoxide reductase
RouteOralOral ScIv or ScOral
Peak plasma levels (healthy volunteers)**0.5 to 2 hours. After surgery: 7 to 9 hours2 to 4 hours3 to 5 hours4 hours1 to 3 hours4 hours
Therapeutic effect in 5 to 7 days
Half-life elimination**115 to 94 to 73 to 41 to 220 to 60
after surgery: 14 to 17after surgery: 7 to 11
Dosing for thromboprophylaxis after orthopedic surgeryInitial: 110 mgInitial: 10 mg30 mg twice daily5,000 IU daily5,000 units every 8 to 12 hoursIndividualized once daily based on target INR 2.5
Maintenance: 220 mg once dailyMaintenance:10 mg once daily