What is the therapeutic International Normalized Ratio (INR) range for adults on warfarin for atrial fibrillation, venous thromboembolism, or mechanical heart valves, and how should low or high INR values be managed?

Therapeutic INR Management for Warfarin

For adults on warfarin, the therapeutic INR range is 2.0-3.0 for atrial fibrillation and venous thromboembolism, and 2.5-3.5 for mechanical mitral valves or older valve types; when INR falls 0.5 below target as a single isolated value, continue the current dose and recheck in 1-2 weeks without bridging therapy. 1, 2

Standard Therapeutic INR Ranges by Indication

Atrial Fibrillation:

• Target INR of 2.5 with therapeutic range 2.0-3.0 for stroke prevention 2
• This applies to both valvular and non-valvular atrial fibrillation 2
• Patients age >75 years may target 2.0-2.5 or even 1.5-2.0 due to increased intracranial bleeding risk, though this lower range provides less stroke protection 3

Venous Thromboembolism (DVT/PE):

• Target INR of 2.5 with therapeutic range 2.0-3.0 for all treatment durations 2
• Duration: 3 months for provoked VTE, 6-12 months for unprovoked first episode, indefinite for recurrent events 2

Mechanical Heart Valves:

• Bileaflet aortic valve (e.g., St. Jude Medical): Target INR 2.5, range 2.0-3.0 2
• Tilting disk or bileaflet mitral valve: Target INR 3.0, range 2.5-3.5 2
• Caged ball or caged disk valves: Target INR 3.0, range 2.5-3.5 plus aspirin 75-100 mg daily 2
• Bioprosthetic valves require INR 2.0-3.0 only for first 3 months post-insertion 2

Management of Subtherapeutic INR

Single Isolated Low INR (0.5 below therapeutic range):

• Continue the current warfarin dose without adjustment 1
• Recheck INR in 1-2 weeks to exclude progressive deviation 1
• Evidence shows no difference in outcomes between dose adjustment versus continuing same dose (44% vs 40% out of range at 2 weeks, OR 1.17,95% CI 0.59-2.30) 1

Bridging Therapy for Low INR:

• Do not routinely bridge with heparin or LMWH for a single subtherapeutic INR (Grade 2C recommendation) 1
• Retrospective data in 2,597 patients showed no significant difference in thromboembolic events between low-INR and therapeutic-INR cohorts 1
• In 294 mechanical valve patients, thromboembolism incidence was 0.3% overall and 0.4% in non-bridged patients 1
• Consider bridging only for extremely high-risk scenarios: mechanical mitral valve with recent thromboembolism within 3 months or history of thromboembolism while anticoagulated 4

Persistent Subtherapeutic INR Requiring Dose Adjustment:

• Increase weekly warfarin dose by 5-20% (typically 10-20%) 5, 4, 6
• Recheck INR within 3-7 days after adjustment 5, 4
• Investigate causes: increased dietary vitamin K, medication non-adherence, drug interactions, malabsorption 4, 6
• Monitor 2-4 times weekly during adjustment period until therapeutic for 2 consecutive days 6

Management of Supratherapeutic INR

INR 3.0-5.0 without bleeding:

• Withhold one dose or reduce daily dose 5
• Resume at lower dose when INR trends toward therapeutic range 5
• No vitamin K needed 4

INR 4.0-5.0 without bleeding:

• Reduce or omit next warfarin dose 2
• Resume at lower dose when INR approaches therapeutic range 2

INR 5.0-9.0 without bleeding:

• Omit 1-2 doses of warfarin 5
• For patients at increased bleeding risk: give oral vitamin K 1.0-2.5 mg 1, 5
• Expected INR reduction within 24 hours 1

INR >9.0 without bleeding:

• Give oral vitamin K 3-5 mg 5
• Expected INR reduction within 24-48 hours 5
• If INR remains high at 24 hours, give additional 1.0-2.0 mg oral vitamin K 1

Serious bleeding or life-threatening overdose:

• Vitamin K 10 mg by slow IV infusion over 30 minutes 5
• Plus fresh frozen plasma or prothrombin complex concentrate 5
• Caution: High-dose vitamin K (10 mg) may cause warfarin resistance lasting up to one week 5

INR Monitoring Schedule

Initiation phase:

• Check INR daily until therapeutic range reached and sustained for 2 consecutive days 1, 5
• Then 2-3 times weekly for 1-2 weeks 1, 5
• Then weekly for 1 month 1, 5

Stable maintenance:

• Every 1-2 months (up to 4 weeks minimum) when consistently therapeutic 1, 5
• Some sources suggest intervals up to 12 weeks for highly stable patients 5

Increased monitoring required during:

• Medication changes (especially antibiotics, NSAIDs) 1, 4
• Dietary changes or weight fluctuations 1, 4
• Intercurrent illness or fever 1, 4
• Any signs of bleeding 1, 4
• After any dose adjustment 6

Critical Clinical Pearls

Bleeding risk:

• Risk increases exponentially when INR exceeds 4.0 and becomes clinically unacceptable above 5.0 5, 3
• Most bleeding events occur even with careful INR control; in one study, 75% of major bleeds occurred when last INR was <3.0 7
• Age >65 years significantly increases bleeding risk, particularly with INR >6.0 6

Thrombotic risk:

• Subtherapeutic anticoagulation (INR <2.0) significantly increases thromboembolism risk 5
• However, half of ischemic strokes occurred when INR was >2.0, suggesting INR control alone cannot prevent all events 7
• In one study, 87% of patients had at least one INR <1.5 and 49% had at least one INR >4.0 during follow-up 7

Time in therapeutic range (TTR):

• Historic TTR poorly predicts future TTR (R² = 0.212, C-index 0.61) 7
• Even historic TTR ≥80% has limited ability to predict future TTR ≥80% 7
• Patients spending <60% of time in therapeutic range should be considered for direct oral anticoagulants (DOACs) instead 6

Post-cardiac surgery considerations:

• Warfarin requirements increase by approximately 26% during first 3 months after valve surgery while mean INR decreases from 2.5 to 2.1 8
• This leads to subtherapeutic anticoagulation with only 48.5% TTR and 40.8% of time spent below INR 2.0 8
• Anticipate need for progressive dose increases during this period 8

Vitamin K supplementation:

• Patients in highest tertile of dietary vitamin K intake have most stable INR control 1
• Daily vitamin K supplementation may improve anticoagulation stability 1