What is the recommended anticoagulation therapy for a patient with atrial fibrillation (AF) and left ventricular dysfunction, considering the results of the RE-LY (Randomized Evaluation of Long-term anticoagulant therapy) trial with dabigatran (Pradaxa)?

Dabigatran for Atrial Fibrillation with Left Ventricular Dysfunction

Dabigatran 150 mg twice daily is recommended as an effective alternative to warfarin for stroke prevention in patients with atrial fibrillation and left ventricular dysfunction (LVEF ≤40%), provided creatinine clearance exceeds 30 mL/min and there is no prosthetic valve or hemodynamically significant valvular disease. 1

Evidence from RE-LY Trial

The RE-LY trial specifically enrolled patients with left ventricular dysfunction as a stroke risk factor, making the results directly applicable to this population:

• Eligible patients included those with LVEF ≤40% or symptomatic heart failure (NYHA class II or higher within 6 months) 1
• The mean CHADS2 score was 2.1, indicating moderate-to-high stroke risk 1
• Median follow-up was 2.0 years with over 18,000 patients enrolled 1

Efficacy Outcomes

Dabigatran 150 mg twice daily demonstrated superior stroke prevention compared to warfarin:

• 34% relative risk reduction in stroke/systemic embolism (1.11% vs 1.71% per year; RR 0.65,95% CI 0.52-0.81; p<0.001) 1
• 74% reduction in intracranial hemorrhage (0.10% vs 0.38% per year; p<0.001) 1
• No increase in major bleeding (3.32% vs 3.57% per year; p=0.32) 1
• Similar mortality rates to warfarin 1

The absolute risk reduction translates to preventing 6 strokes per 1,000 patient-years of treatment 1.

Safety Profile

Major bleeding considerations:

• Overall major bleeding rates were similar between dabigatran 150 mg and warfarin 1
• Gastrointestinal bleeding was 50% higher with dabigatran (1.59% vs 1.05% per year) 1, 2
• Dyspepsia occurred in 11-12% of patients on dabigatran versus 5.8% on warfarin 1
• Life-threatening bleeding, intracranial bleeding, and total bleeding were all reduced with dabigatran 1

Dosing Algorithm Based on Renal Function

Standard dose (CrCl >30 mL/min):

• Dabigatran 150 mg orally twice daily 1

Moderate renal impairment (CrCl 30-50 mL/min) with P-gp inhibitors:

• Reduce to 75 mg twice daily if taking dronedarone or systemic ketoconazole 1, 3, 2

Severe renal impairment (CrCl 15-30 mL/min):

• Reduce to 75 mg twice daily, though this dose was never tested in RE-LY 1, 3

CrCl <15 mL/min:

• Dabigatran is contraindicated 1, 2

Absolute Contraindications

Do not use dabigatran in patients with: 1, 2

• Prosthetic heart valves
• Hemodynamically significant valvular disease (particularly mitral stenosis)
• Severe renal failure (CrCl <15 mL/min)
• Advanced liver disease with impaired baseline clotting function
• Active pathological bleeding

Age-Related Considerations

For patients ≥75 years:

• Intracranial bleeding risk remains lower with dabigatran regardless of age 4
• Extracranial bleeding risk is higher in elderly patients (5.10% vs 4.37% per year for age ≥75) 4
• The stroke prevention benefit persists across all age groups 4
• Renal function must be assessed at least annually, more frequently if clinical deterioration occurs 3

Clinical Decision Points

Dabigatran is preferred over warfarin when:

• Patient has difficulty maintaining therapeutic INR (time in therapeutic range <65-70%) 3
• Patient cannot access reliable INR monitoring 5
• Patient prefers to avoid dietary restrictions and frequent monitoring 5, 6

Warfarin may be preferred when:

• Patient already has excellent INR control (time in therapeutic range >65-70%) 3
• Patient cannot comply with twice-daily dosing 5, 6
• Cost is prohibitive 5
• Patient is ≥80 years with high gastrointestinal bleeding risk 3

Monitoring Requirements

Before initiating dabigatran: 3, 6

• Calculate creatinine clearance using Cockcroft-Gault formula
• Assess for contraindications (valvular disease, liver disease, bleeding disorders)
• Review all medications for P-gp inhibitors

During treatment: 3

• Reassess renal function at least annually
• Monitor for signs of bleeding, particularly gastrointestinal symptoms
• No routine coagulation monitoring required

Critical Safety Warnings

A small but statistically non-significant increase in myocardial infarction was observed (0.81% vs 0.64% per year; RR 1.27,95% CI 0.94-1.71; p=0.12) 1. This finding remains of uncertain clinical significance but should be considered in patients with recent acute coronary syndrome.

When transitioning from warfarin to dabigatran, do not start dabigatran until INR falls below 2.0 to avoid overlapping anticoagulation and increased bleeding risk 3.

Dabigatran should not be started within 14 days of acute stroke; consider bridging with parenteral anticoagulation first 3.