Therapeutic Anticoagulation Range
For warfarin therapy, maintain an INR of 2.0-3.0 for most indications including atrial fibrillation and venous thromboembolism, ensuring time in therapeutic range (TTR) exceeds 70% for optimal safety and effectiveness. 1
Warfarin (Vitamin K Antagonist) Therapeutic Targets
INR Range by Indication
- Standard target INR: 2.0-3.0 for atrial fibrillation, venous thromboembolism, and most thromboembolic conditions 1
- Higher target INR: 2.5-3.5 for mechanical mitral valves or older mechanical valve types 2
- Bileaflet mechanical aortic valves typically require the standard 2.0-3.0 range 2
Time in Therapeutic Range (TTR) Requirements
The TTR threshold is as clinically important as the INR target itself. 3
- TTR ≥70% is the quality benchmark for warfarin therapy to ensure both safety and effectiveness 1, 3
- TTR between 65-70% indicates borderline control requiring intensified monitoring and patient education 3
- TTR <65-70% mandates switching to a DOAC in eligible patients to prevent thromboembolism and intracranial hemorrhage 1, 3
Critical Implementation Details
- INR checks should occur at appropriate frequency based on stability, with more frequent monitoring when TTR falls below target 1, 3
- TTR must be calculated using the Rosendaal method, not simply counting "INRs in range" 3
- Patient education and counseling about consistent dietary vitamin K intake are essential for maintaining stable INR 1, 3
Direct Oral Anticoagulants (DOACs) - No INR Monitoring Required
DOACs are recommended in preference to warfarin for stroke prevention in atrial fibrillation, except in patients with mechanical heart valves or moderate-to-severe mitral stenosis. 1
Standard Full Doses (No Routine Monitoring)
Apixaban: 1
- Standard dose: 5 mg twice daily
- Reduced dose: 2.5 mg twice daily ONLY if patient meets 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, serum creatinine ≥133 μmol/L
- Standard dose: 150 mg twice daily
- Reduced dose: 110 mg twice daily if age ≥80 years OR receiving concomitant verapamil
- Consider dose reduction for age 75-80, moderate renal impairment (CrCl 30-50 mL/min), gastritis/esophagitis, or increased bleeding risk
Rivaroxaban: 1
- Standard dose: 20 mg once daily
- Reduced dose: 15 mg once daily if CrCl 30-49 mL/min
Edoxaban: 1
- Standard dose: 60 mg once daily
- Reduced dose: 30 mg once daily if CrCl 15-50 mL/min, body weight ≤60 kg, or receiving P-glycoprotein inhibitors
Critical DOAC Prescribing Principles
- Reduced-dose DOAC therapy is NOT recommended unless patients meet DOAC-specific criteria to prevent underdosing and avoidable thromboembolic events 1
- No routine coagulation monitoring is required or recommended 5, 6
- Renal function must be monitored as impairment increases bleeding risk and affects drug clearance 1, 7
Common Pitfalls to Avoid
- Do not accept marginal TTR values (60-65%) as adequate for warfarin therapy; this represents suboptimal anticoagulation 3
- Do not arbitrarily reduce DOAC doses without meeting specific criteria, as this leads to preventable strokes 1
- Do not delay switching from warfarin to DOAC in eligible patients with persistently low TTR despite interventions 1, 3
- Do not confuse TTR with simply having "most INRs in range"; proper calculation using the Rosendaal method is required 3
- For patients ≥75 years on stable warfarin with polypharmacy, maintaining VKA rather than switching may be considered to prevent excess bleeding risk 1
Superiority of DOACs Over Warfarin
Meta-analysis of 71,683 patients demonstrated that standard-dose DOACs compared with warfarin reduce: 1
- Stroke or systemic embolism (HR 0.81,95% CI 0.73-0.91)
- All-cause mortality (HR 0.90,95% CI 0.85-0.95)
- Intracranial hemorrhage by 50% (HR 0.48,95% CI 0.39-0.59)
- No significant difference in other major bleeding (HR 0.86,95% CI 0.73-1.00)