What is the target International Normalized Ratio (INR) range for anticoagulation therapy in adults with a history of deep vein thrombosis, pulmonary embolism, or atrial fibrillation?

Target INR for Thrombosis Anticoagulation

For adults with deep vein thrombosis, pulmonary embolism, or atrial fibrillation requiring warfarin therapy, target an INR of 2.5 with a therapeutic range of 2.0-3.0. 1, 2

Therapeutic Range by Indication

Deep Vein Thrombosis and Pulmonary Embolism

• Target INR of 2.5 (range 2.0-3.0) is recommended for all patients with DVT or PE treated with warfarin. 1, 2
• This range provides maximum protection against recurrent thrombosis while minimizing bleeding risk. 3
• Lower intensity anticoagulation (INR 1.5-1.9) significantly increases recurrent thrombosis risk and should be avoided. 1, 4
• Higher intensity anticoagulation (INR 3.1-4.0) increases bleeding without additional efficacy benefit. 3

Atrial Fibrillation

• Target INR of 2.5 (range 2.0-3.0) is the standard for nonvalvular atrial fibrillation. 1
• Maximum stroke protection is achieved with INR 2.0-3.0, while INR 1.6-2.5 provides only approximately 80% of the efficacy. 1
• The optimal benefit-risk balance occurs between INR 2.0-2.5, where ischemic stroke risk is minimized without excessive intracranial hemorrhage. 5
• For patients ≥75 years old, some experts suggest a target INR of 2.0 (range 1.6-2.5) to reduce bleeding risk, though this remains controversial. 1
• The 2018 CHEST guideline explicitly recommends against lower INR targets (such as 1.6-2.6) globally, stating the conventional INR target of 2.0-3.0 should be employed. 1

Warfarin Initiation and Bridging Protocol

Starting Therapy

• Begin warfarin simultaneously with parenteral anticoagulation (unfractionated heparin or LMWH) on day 1 of treatment. 1, 4, 2
• Overlap parenteral anticoagulation for a minimum of 5 days AND until INR ≥2.0 for at least 24 consecutive hours before discontinuing heparin. 1, 4, 2
• Both conditions must be met—the 5-day minimum and therapeutic INR for 24 hours—before stopping parenteral therapy. 2

Critical Pitfall to Avoid

• Never discontinue heparin prematurely before meeting both criteria (5 days AND INR ≥2.0 for 24 hours). 4, 2
• Warfarin initially creates a prothrombotic state through rapid protein C depletion before achieving therapeutic anticoagulation, making adequate bridging essential. 4

Monitoring Schedule

Initial Phase

• Check INR daily or every other day during titration until therapeutic range is achieved. 4
• After stabilization in therapeutic range, monitor INR weekly for 2-3 weeks. 4

Maintenance Phase

• Time in therapeutic range (TTR) should be ≥65-70% for optimal efficacy and safety. 1
• Patients with TTR <65% have significantly higher rates of stroke/systemic embolism (HR 2.55), all-cause mortality (HR 2.39), and major bleeding (HR 1.54) compared to those with TTR ≥65%. 1

Action Required for Suboptimal INR Control

• If TTR is <65-70%, implement more frequent INR testing, review medication adherence, address factors influencing INR control, provide patient education, or consider switching to a direct oral anticoagulant (DOAC). 1

Duration of Anticoagulation

Provoked DVT/PE (Reversible Risk Factor)

• Discontinue anticoagulation after 3 months for first-episode DVT/PE related to major reversible risk factors (surgery, trauma). 1, 3

Unprovoked DVT/PE

• Continue anticoagulation for at least 6 months, then consider indefinite therapy with periodic risk-benefit reassessment. 1
• Patients with unprovoked VTE should receive indefinite antithrombotic therapy unless high bleeding risk exists. 1

Recurrent VTE

• Indefinite anticoagulation is recommended with periodic reassessment. 1

Cancer-Associated Thrombosis

• LMWH monotherapy is preferred over warfarin for at least 3-6 months or as long as cancer/chemotherapy is ongoing. 1
• If LMWH is not feasible, warfarin with target INR 2.0-3.0 is a reasonable alternative. 1

Special Populations

Mechanical Heart Valves

• Higher intensity anticoagulation (INR 2.5-3.5) is required for bileaflet or tilting disc valves. 6
• Caged ball or caged disc valves require even higher target INR. 6

Breakthrough Thrombosis on Warfarin

• For patients who develop DVT/PE while on therapeutic warfarin, switch to LMWH rather than DOAC. 1

Alternative to Warfarin

Direct Oral Anticoagulants (DOACs)

• DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) are preferred over warfarin for VTE treatment in patients without cancer. 1
• DOACs offer equivalent efficacy with lower bleeding risk and do not require INR monitoring. 1
• For secondary prevention after completing primary treatment, either standard-dose or lower-dose DOAC regimens may be used (rivaroxaban 10 mg daily or apixaban 2.5 mg twice daily). 1