From the Guidelines
When switching from warfarin to dabigatran, the timing depends on the patient's current INR level, and it is recommended to wait until the INR falls to about 2.0 before starting dabigatran, as stated in the 2012 focused update of the ESC guidelines for the management of atrial fibrillation 1.
Key Considerations
- The standard dabigatran dosing is typically 150 mg twice daily for most patients with atrial fibrillation, but should be reduced to 110 mg twice daily (or 75 mg twice daily in the US) for patients with moderate renal impairment (CrCl 30-50 mL/min), those aged 75 or older, or patients with high bleeding risk, as recommended in the 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation 2.
- Dabigatran should be taken with food to reduce gastrointestinal side effects, and patients should be advised that unlike warfarin, regular INR monitoring is not required.
- The transition approach is necessary because warfarin has a longer half-life and works by inhibiting vitamin K-dependent clotting factors, while dabigatran is a direct thrombin inhibitor with a more rapid onset and offset of action, as explained in the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation 3.
Patient Selection
- Selection of patients with AF and at least 1 additional risk factor for stroke who could benefit from treatment with dabigatran as opposed to warfarin should consider individual clinical features, including the ability to comply with twice-daily dosing, availability of an anticoagulation management program to sustain routine monitoring of INR, patient preferences, cost, and other factors, as stated in the 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation 2.
- Patients already taking warfarin with excellent INR control may have little to gain by switching to dabigatran, as noted in the 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation 2.
Safety and Efficacy
- Dabigatran has been shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular AF, with a lower risk of intracranial bleeding compared to warfarin, as demonstrated in the RE-LY trial 2, 3.
- However, dabigatran may increase the risk of gastrointestinal bleeding, particularly at the higher dose of 150 mg twice daily, as reported in the RE-LY trial 2, 3.
Monitoring and Follow-up
- Regular monitoring of renal function is recommended for patients taking dabigatran, as it is renally excreted and may require dose adjustment in patients with moderate renal impairment, as stated in the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation 3.
- Patients should be advised to seek medical attention immediately if they experience any signs or symptoms of bleeding, as dabigatran has a rapid onset and offset of action and may increase the risk of bleeding, as noted in the 2012 focused update of the ESC guidelines for the management of atrial fibrillation 1.
From the FDA Drug Label
When converting patients from warfarin therapy to dabigatran etexilate capsules, discontinue warfarin and start dabigatran etexilate capsules when the INR is below 2. 0. When converting from dabigatran etexilate capsules to warfarin, adjust the starting time of warfarin as follows: Adults For CrCl ≥50 mL/min, start warfarin 3 days before discontinuing dabigatran etexilate capsules. For CrCl 30 to 50 mL/min, start warfarin 2 days before discontinuing dabigatran etexilate capsules For CrCl 15 to 30 mL/min, start warfarin 1 day before discontinuing dabigatran etexilate capsules. For CrCl <15 mL/min, no recommendations can be made.
The considerations for switching from Warfarin to Dabigatran include:
- Discontinuing Warfarin and starting Dabigatran when the INR is below 2.0. The considerations for switching from Dabigatran to Warfarin include:
- Renal function: The timing of starting Warfarin depends on the patient's CrCl:
- For CrCl ≥50 mL/min, start Warfarin 3 days before discontinuing Dabigatran.
- For CrCl 30 to 50 mL/min, start Warfarin 2 days before discontinuing Dabigatran.
- For CrCl 15 to 30 mL/min, start Warfarin 1 day before discontinuing Dabigatran.
- For CrCl <15 mL/min, no recommendations can be made. 4
From the Research
Considerations for Switching from Warfarin to Dabigatran
- The decision to switch from warfarin to dabigatran should be based on individual patient characteristics, such as renal function and risk of thrombosis 5, 6.
- Dabigatran has been shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, but it may not be suitable for all patients, particularly those with severe renal or hepatic impairment 7.
- Patients with a high risk of thrombosis and good INR control on warfarin may not benefit from switching to dabigatran, as the difference in favor of dabigatran was no longer statistically significant in this population 5.
- The risk of bleeding, particularly gastrointestinal bleeding, is higher with dabigatran than with warfarin, especially in patients with renal impairment 6.
- Dabigatran does not require monitoring of haemostasis, but renal function must be monitored, as renal impairment increases the risk of bleeding 5.
- The effects of dabigatran are potentiated by combination with P-glycoprotein inhibitors and drugs that impair renal function, and combination with other antithrombotic agents should be avoided 5.
- Dyspepsia is more frequent with dabigatran than with warfarin, and hepatic adverse effects appear to be mild but need to be monitored 5.
- There is no antidote for dabigatran overdose, unlike vitamin K antagonists, which can be reversed with vitamin K 5.
Patient-Specific Considerations
- A patient-specific approach involving the perspectives of informed patients is most reasonable when deciding whether to switch from warfarin to dabigatran 8.
- Patients who are warfarin-naive, difficult to maintain in therapeutic range, or at risk of warfarin-related bleeding complications may be suitable candidates for dabigatran 9.
- However, the frequency of initial prescription of dabigatran for stroke prevention in AF and the frequency of transition from warfarin to dabigatran have been less than expected, suggesting that warfarin remains a viable option for many patients 9.