| Attribute | Warfarin | Dabigatran |
|---|---|---|
| Administration | Oral | Oral |
| Mechanism of action | Inhibition of vitamin-K-dependent coagulation factors (II, VII, IX, X, and protein C and S) | Inhibition of thrombin |
| Oral bioavailability | 100% | 6.5% |
| Half-life | 20-60 hours | 12-17 hours |
| Metabolism | Hepatic | Renal (80%) |
| Time to onset | 24-72 hours | 1-2 hours |
| Protein binding | 99% | 35% |
| Antagonist | Vitamin K | None |
| Laboratory monitoring | Required | None required |
| Dose adjustment | Required for each individual | Reduction only for creatinine clearance of 15-30 mL/min |
| Interaction with diet | Interacts with foods rich in vitamin K (eg, cabbage, spinach) | No interaction with foods rich in vitamin K |
| Interaction with drugs | Interacts with amiodarone, antifungals, antibiotics, and alcohol, which may require dose adjustments of either warfarin or the concomitant agent | Dose adjustment of dabigatran may be required with ketoconazole and dronedarone |
Cost-effectiveness of dabigatran
The prescription cost of dabigatran is a lot higher than warfarin, although a recent study demonstrated its cost-effectiveness through a reduction in the need for laboratory monitoring and decreased complications due to over-and under-anticoagulation.33
Factors that come into play
Dabigatran is an alternative to warfarin for long-term anticoagulation in patients with nonvalvular AF who are at a higher risk of stroke with a CHADS2 score of ≥1 or systemic thromboembolism.18 While the main benefits of dabigatran are a quick onset of action, no need for laboratory monitoring, rare interactions with drugs and food, and a decrease in intracranial bleeding compared with warfarin, it did cause more gastrointestinal adverse effects, including bleeding, than warfarin in the RE-LY trial.
Dabigitran was also associated with a higher incidence of MI in RE-LY and an increased risk of MI or acute coronary syndrome in the meta-analysis, but the absolute risk increase in both cases was very small.21-23 Thus, for many patients, the choice of anticoagulant depends on individual preference and ability to comply with a twice-daily dosing regimen, availability of INR monitoring, and cost of treatment.34
Patients who should not receive dabigatran
Dabigatran is contraindicated for patients with a creatinine clearance <15 mL/min, a prosthetic valve, significant valve disease, a history of serious allergic reaction to the drug, or a high risk of bleeding (eg, from recurrent falls, bleeding peptic ulcer).35
Initiating dabigatran therapy
Start dabigatran at a dose of 150 mg twice daily if the creatinine clearance is >30 mL/min, or at 75 mg twice daily if creatinine clearance is 15 to 30 mL/min. In switching a patient from parenteral anticoagulation, you may start dabigatran ≤2 hours before the next scheduled dose of the parenteral agent (eg, low-molecular-weight heparin) or the termination of a continuously administered agent (eg, unfractionated heparin). For patients taking warfarin, withhold dabigatran until the INR is <2.29
Thrombin time is the most reliable measure of drug effect
Dabigatran has a variable and unpredictable effect on the INR, which should not be used to measure the drug’s anticoagulation effect. While therapeutic concentrations modestly elevate the INR, there have been some reports of significant INR elevation.29 However, lab results with the ecarin clotting test (ECT) or thrombin time (TT) correlate well with dabigatran serum concentrations. ECT is primarily a research tool and not commonly available in hospitals; TT, however, is readily available. Activated partial thromboplastin time (aPTT), also commonly available, is prolonged in a nonlinear fashion with dabigatran use. None of these tests has been systematically studied and correlated with clinical outcomes of dabigatran use.29
Adverse effects to watch for
In the RE-LY study, dyspepsia was the most commonly reported adverse effect of dabigatran (11%).21 As with warfarin, other adverse effects, such as dizziness, dyspnea, and fatigue, were reported for dabigatran. Unlike ximelgatran, there is no significant effect on liver enzymes. There is, however, a risk of major and minor bleeding complications.
Bleeding with dabigatran. In the event of a bleeding complication, discontinue dabigatran. There is no specific antidote for this drug; supportive therapy relies on surgical intervention and transfusion of fresh frozen plasma and packed cells. Maintaining adequate diuresis may enhance elimination of the drug. Given dabigatran’s low protein-binding potential, dialysis may be considered; however, data supporting this treatment decision are limited.29
Patients taking dual antiplatelet agents are at a higher risk of bleeding if they also receive either dabigatran or warfarin, although it is not known if one anticoagulant confers a higher risk than the other. In such patients, carefully weigh the risk of bleeding against the benefits of stroke prevention.
Discontinue dabigatran before surgery
Withhold dabigatran from patients scheduled for elective surgery (TABLE 3).29 For those with a high risk of bleeding, measure TT 6 to 12 hours before the procedure to ensure normalization of the value. An acceptable alternative measure, although less precise, is the aPTT. For emergency procedures, fresh frozen plasma may be used to acutely reverse the drug’s effect.