What is Pradaxa (dabigatran) used for?

What is Pradaxa Used For?

Pradaxa (dabigatran) is primarily used to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation who have additional stroke risk factors. 1, 2

Primary Indication: Stroke Prevention in Atrial Fibrillation

Dabigatran is approved as an alternative to warfarin for preventing stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation who meet specific criteria 1:

• Patients must have at least one additional stroke risk factor such as prior stroke/TIA, heart failure, hypertension, age ≥75 years, diabetes, or coronary artery disease 1, 2
• The standard dose is 150 mg twice daily for patients with creatinine clearance >30 mL/min, which demonstrated a 34% reduction in stroke/systemic embolism compared to warfarin in the RE-LY trial 2, 3

Mechanism and Advantages

Dabigatran works as a direct thrombin (factor IIa) inhibitor that blocks the coagulation cascade 2:

• No routine INR monitoring required, unlike warfarin 2, 3
• Predictable pharmacokinetics with fixed dosing 1, 2
• 74% reduction in hemorrhagic stroke compared to warfarin 2, 3
• Fewer food and drug interactions because conversion to active drug is independent of cytochrome P-450 1, 2

Critical Contraindications

Dabigatran is absolutely contraindicated in patients with: 1, 4

• Mechanical prosthetic heart valves - the RE-ALIGN trial showed significantly more thromboembolic events and major bleeding with dabigatran versus warfarin in this population 4
• Hemodynamically significant valvular disease (particularly moderate-to-severe mitral stenosis) 1, 5
• Severe renal failure (CrCl <15 mL/min) or end-stage kidney disease on dialysis 1
• Advanced liver disease with impaired baseline clotting function 1, 4
• Active pathological bleeding 4

Renal Function-Based Dosing

Renal function is the primary determinant of dabigatran dosing and safety because 80% is excreted unchanged in urine 2, 3:

• CrCl >30 mL/min: 150 mg twice daily (standard dose) 1, 3
• CrCl 30-50 mL/min with P-gp inhibitors (dronedarone, systemic ketoconazole): reduce to 75 mg twice daily 1, 3, 4
• CrCl 15-30 mL/min: 75 mg twice daily (though this dose was never tested in RE-LY and may be inadequate) 1, 3
• CrCl <15 mL/min or dialysis: contraindicated 1

Important Safety Considerations

Key bleeding risks and management issues 1, 2, 4:

• 50% increase in gastrointestinal bleeding compared to warfarin (1.51% vs 1.12% per year) 3
• No specific antidote available at the time of these guidelines (though idarucizumab is now available) 3, 4
• Hemodialysis can remove dabigatran in cases of life-threatening bleeding 4
• Dyspepsia occurs in 11-12% of patients 3

Clinical Pearls for Patient Selection

Consider these factors when deciding between dabigatran and warfarin 1, 3:

• Patients with excellent INR control on warfarin (time in therapeutic range >65-70%) may have little to gain by switching 3
• Twice-daily dosing compliance is essential due to the 12-17 hour half-life 2, 3
• Assess renal function before initiation and at least annually thereafter 1, 3
• Avoid in triple-positive antiphospholipid syndrome due to increased thrombotic risk with DOACs versus warfarin 4

Additional Approved Indications

Beyond atrial fibrillation, dabigatran is also approved for 6, 7:

• Treatment and reduction of recurrence of deep vein thrombosis and pulmonary embolism in adults 4
• Primary prevention of venous thromboembolism after total hip or knee replacement (approved in EU and other countries) 7, 8