Warfarin INR Targets

Warfarin related Links

Key statements from 9th ACCP guidelines

Indication	INR (range)	Evidence
Optimal Therapeutic INR Range	INR range of 2.0 to 3.0 (target INR of 2.5)	(Grade 1B)
Therapeutic Range for High-Risk Groups –patients with antiphospholipid syndrome with previous arterial or venous thromboembolism	Moderate intensity INR range (INR 2.0-3.0) rather than higher intensity (INR 3.0-4.5)	(Grade 2B)
DVT of the leg	INR range of 2.0 to 3.0 (target INR of 2.5)	(Grade 1B)
PE	INR range of 2.0 to 3.0 (target INR of 2.5)	(Grade 1B)
Patients With AF and Stable Coronary Artery Disease (no acute coronary syndrome within the previous year)	Adjusted-dose warfarin therapy alone – INR range of 2.0 to 3.0 (target INR of 2.5) rather than the combination of adjusted-dose warfarin therapy and aspirin	(Grade 2C)
Mechanical mitral valve	INR target of 3.0 (range, 2.5-3.5)	(Grade 2C)
Intensity of Warfarin Therapy in Patients With Double Mechanical Valve or With Additional Risk Factors (mechanical heart valves in both the aortic and mitral position)	INR target of 3.0 (range 2.5-3.5)	(Grade 2C)
Bioprosthetic valve in the mitral position	Target INR, 2.5; range, 2.0-3.0) over no warfarin therapy for the first 3 months after valve insertion	(Grade 2C)
Prevention of Recurrent VTE in Pregnant Women	Postpartum prophylaxis for 6 weeks with prophylactic- or intermediate-dose LMWH or warfarin targeted at INR 2.0 to 3.0 rather than no prophylaxis	(Grade 2B)

For additional guidance please review:

Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3.

Statements from previous guidelines:

Venous Thromboembolism (including [DVT] and PE)

Adjust the warfarin dose to maintain a target INR of 2.5 (INR range, 2.0-3.0) for all treatment durations. The duration of treatment is based on the indication as follows:

For patients with a DVT or PE secondary to a transient (reversible) risk factor, treatment with warfarin for 3 months is recommended.
For patients with an unprovoked DVT or PE, treatment with warfarin is recommended for at least 3 months. After 3 months of therapy, evaluate the risk-benefit ratio of long-term treatment for the individual patient.
For patients with two episodes of unprovoked DVT or PE, long-term treatment with warfarin is recommended. For a patient receiving long-term anticoagulant treatment, periodically reassess the risk-benefit ratio of continuing such treatment in the individual patient.

Atrial Fibrillation

In patients with non-valvular AF, anticoagulate with warfarin to target INR of 2.5 (range, 2.0-3.0).

In patients with non-valvular AF that is persistent or paroxysmal and at high risk of stroke (i.e., having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, or 2 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended.
In patients with non-valvular AF that is persistent or paroxysmal and at an intermediate risk of ischemic stroke (i.e., having 1 of the following risk factors: age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus), long-term anticoagulation with warfarin is recommended.
For patients with AF and mitral stenosis, long-term anticoagulation with warfarin is recommended.
For patients with AF and prosthetic heart valves, long-term anticoagulation with warfarin is recommended; the target INR may be increased and aspirin added depending on valve type and position, and on patient factors.

Mechanical and Bioprosthetic Heart Valves

For patients with a bileaflet mechanical valve or a Medtronic Hall (Minneapolis, MN) tilting disk valve in the aortic position who are in sinus rhythm and without left atrial enlargement, therapy with warfarin to a target INR of 2.5 (range, 2.0-3.0) is recommended.
For patients with tilting disk valves and bileaflet mechanical valves in the mitral position, therapy with warfarin to a target INR of 3.0 (range, 2.5-3.5) is recommended.
For patients with caged ball or caged disk valves, therapy with warfarin to a target INR of 3.0 (range, 2.5-3.5) is recommended.
For patients with a bioprosthetic valve in the mitral position, therapy with warfarin to a target INR of 2.5 (range, 2.0-3.0) for the first 3 months after valve insertion is recommended. If additional risk factors for thromboembolism are present (AF, previous thromboembolism, left ventricular dysfunction), a target INR of 2.5 (range, 2.0-3.0) is recommended.

Post-Myocardial Infarction

For high-risk patients with MI (e.g., those with a large anterior MI, those with significant heart failure, those with intracardiac thrombus visible on transthoracic echocardiography, those with AF, and those with a history of a thromboembolic event), therapy with combined moderate-intensity (INR, 2.0-3.0) warfarin plus low-dose aspirin (≤100 mg/day) for at least 3 months after the MI is recommended.

Recurrent Systemic Embolism and Other Indications

Oral anticoagulation therapy with warfarin has not been fully evaluated by clinical trials in patients with valvular disease associated with AF, patients with mitral stenosis, and patients with recurrent systemic embolism of unknown etiology. However, a moderate dose regimen (INR 2.0-3.0) may be used for these patients.

Condition	Targeted INR
Acute myocardial infarction (high-risk): High-risk includes a large anterior MI, significant heart failure, intracardiac thrombus, thromboembolism	Range: 2.0 -3.0 Targeted INR: 2.5Combine with aspirin 81 mg/day. Maintain anticoagulation for at least 3 months.
Antiphospholipid Syndrome (no other risk factors):	Range: 2.0 -3.0 Targeted INR: 2.5 Treatment length: lifetime
Antiphospholipid Syndrome and recurrent thromboembolism:	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime
Bioprosthetic (tissue) Valve • Mitral Valve (MVR):	Goal INR 2.5: range, 2.0 – 3.0; duration 3 months and then aspirin therapy (81mg/d)
Bioprosthetic (tissue) Valve • Aortic Valve (AVR). NSR. no other indication for warfarin therapy	ASA (50 to 100 mg/day)
Bioprosthetic (tissue) Valve -history of systemic embolism	Range: 2.0 -3.0 Targeted INR: 2.5 Treatment length: for at least 3 months after valve insertion, followed by clinical reassessment
Bioprosthetic (tissue) Valve -additional risk factors for thromboembolism, including AF, hypercoagulable state, or low ejection fraction	Range: 2.0 -3.0 Targeted INR: 2.5Chest guidelines³: low-dose aspirin (50 to 100 mg/d) should be considered, particularly in patients with history of atherosclerotic vascular disease. Omit ASA in patients with bioprosthetic heart valves who are at particularly high risk of bleeding, such as in patients with history of GI bleed or in patients > 80 years of age
Patients with MVP who have AF, documented systemic embolism, or recurrent TIAs despite ASA therapy:	Range: 2.0 -3.0 Targeted INR: 2.5
Rheumatic mitral valve disease with AF who suffer systemic embolism or have left atrial thrombus while receiving warfarin at a therapeutic INR	Add low-dose ASA (50 to 100 mg/d) after consideration of the additional hemorrhagic risk. Alternative strategy: adjustment of warfarin dosing to achieve a higher target INR (target INR, 3.0; range, 2.5 to 3.5).
Rheumatic mitral valve disease complicated singly or in combination by the presence of AF, previous systemic embolism, or left atrial thrombus	Range: 2.0 -3.0 Targeted INR: 2.5
Rheumatic mitral valve disease and normal sinus rhythm with a left atrial diameter > 55 mm	Range: 2.0 -3.0 Targeted INR: 2.5
Venous thromboembolism:	Range: 2.0 -3.0 Targeted INR: 2.5 Treatment length: variable
Mechanical Prosthetic Valve:
Bileaflet mechanical valve in the aortic position, left atrium of normal size, NSR, normal ejection fraction	Range: 2.0 -3.0 Targeted INR: 2.5 Treatment length: lifetime
Bileaflet mechanical aortic valve and Thromboembolism Risk Factors (AF)	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime
First generation aortic valve (i.e. caged ball or caged disk)	INR range: 2.5-3.5 Targeted INR: 3.0
Mitral Valve (MVR) – all mitral valves with or without risk factors for thromboembolism	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime
St Jude Medical bileaflet mechanical aortic valve:	Range: 2.0 -3.0 Targeted INR: 2.5 Treatment length: lifetime
Tilting disk valve or bileaflet mechanical valve in the mitral position	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime
Modern aortic valve with atrial fibrillation or other risk factor(s) for thromboembolism¹ -Carbomedics bileaflet -Medtronic Hall tilting disk	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime
CarboMedics bileaflet valves or Medtronic Hall tilting disk mechanical valve in the aortic position, normal left atrium, and sinus rhythm	Range: 2.0 -3.0 Targeted INR: 2.5 Treatment length: lifetime
Mechanical prosthetic valve with systemic embolism despite adequate anticoagulation:	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime Combine with aspirin 81 mg/dayChest guidelines³: “In patients with mechanical prosthetic heart valves who have systemic embolism despite a therapeutic INR, we suggest the addition of ASA (50 to 100 mg/d) if not previously provided and/or upward titration of warfarin therapy to achieve a higher target INR. For a previous target INR of 2.5, we suggest the warfarin dose be increased to achieve a target INR of 3.0 (range, 2.5 to 3.5). For a previous target INR of 3.0, we suggest the warfarin dose be increased to achieve a target INR of 3.5 (range, 3.0 to 4.0) [Grade 2C].”
Mechanical valve and risk factors (atrial fibrillation, MI, left atrial enlargement, low EF, endocardial damage)	INR range: 2.5-3.5 Targeted INR: 3.0 Treatment length: lifetime Combine with aspirin 81 mg/day unless patient at particularly high risk of bleeding, such as in patients with history of GI bleed, or in patients > 80 years of age

1. Thromboembolism Risk Factors:
• Atrial fibrillation
• Left atrium enlargement
• Low left-ventricular ejection fraction
• Age < 70
• Prior thromboembolism
• Hypercoagulable state

References:

1. Ansell J, Hirsh J, Hylek E, Jacobson A, et al. Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 (suppl 6);133:160s-198s.

2. Package insert data.

3. Salem DN, O’Gara PT, C, Pauker SG. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008 Jun;133(6 Suppl):593S-629S.