What are the guidelines for anticoagulation therapy in patients with atrial fibrillation (AF) and high stroke risk or a history of venous thromboembolism (VTE)?

Anticoagulation Guidelines for Atrial Fibrillation and Venous Thromboembolism

Direct Oral Anticoagulants (DOACs) Are First-Line for Non-Valvular Atrial Fibrillation

For patients with non-valvular atrial fibrillation at elevated stroke risk, direct oral anticoagulants (DOACs) are recommended over warfarin, with apixaban 5 mg twice daily as the preferred agent due to superior efficacy and safety. 1, 2

Risk Stratification for Atrial Fibrillation

• Use the CHA₂DS₂-VASc score to determine anticoagulation need: A score of ≥2 in men or ≥3 in women indicates high stroke risk requiring oral anticoagulation 1, 2

• For CHA₂DS₂-VASc score of 0 in men or 1 in women: No anticoagulation is recommended 1, 2

• For CHA₂DS₂-VASc score of 1 in men or 2 in women: Oral anticoagulation is preferred over no therapy 1, 2

• The scoring system includes: Congestive heart failure (1 point), hypertension (1 point), age ≥75 years (2 points), diabetes (1 point), prior stroke/TIA (2 points), vascular disease (1 point), age 65-74 years (1 point), and female sex (1 point) 2

DOAC Selection Algorithm

First-line choice: Apixaban 5 mg twice daily for most patients with non-valvular AF 1, 2

For patients with prior gastrointestinal bleeding: Apixaban 5 mg twice daily or dabigatran 110 mg twice daily (where available) are preferable as they do not increase GI bleeding risk compared to warfarin 1, 2

For patients at high risk of ischemic stroke with low bleeding risk: Dabigatran 150 mg twice daily may be considered as it is the only agent with superior efficacy compared to warfarin 1, 2

For patients with high bleeding risk: Apixaban 5 mg twice daily, edoxaban 60 mg once daily, or dabigatran 110 mg twice daily are recommended to reduce major bleeding 1, 2

Critical Contraindications

• DOACs are contraindicated in patients with mechanical heart valves or moderate-to-severe mitral stenosis - warfarin is required 1

• Dabigatran should not be used with mechanical heart valves due to increased thrombotic and bleeding risk 1

• Dabigatran and rivaroxaban are not recommended in end-stage chronic kidney disease (CrCl <15 mL/min) or dialysis due to lack of safety data 1

Warfarin Management When DOACs Are Not Suitable

When vitamin K antagonists (VKAs) are used, target INR should be 2.0-3.0 with time in therapeutic range (TTR) ideally ≥70%. 1, 3

Warfarin Dosing by Indication

• Non-valvular AF: INR 2.0-3.0 1, 3

• Mechanical prosthetic valves: INR depends on valve type and position - St. Jude Medical bileaflet valve in aortic position requires INR 2.0-3.0; tilting disk and bileaflet valves in mitral position require INR 2.5-3.5; caged ball/disk valves require INR 2.5-3.5 plus aspirin 75-100 mg daily 3

• Venous thromboembolism: INR 2.0-3.0 for all treatment durations 3

Managing Suboptimal INR Control

If TTR is <65-70%, implement the following measures: 1

• Increase frequency of INR monitoring
• Review medication adherence
• Address factors affecting INR control (diet, drug interactions)
• Provide patient education and counseling
• Consider switching to a DOAC if TTR remains <70% 1, 2

Use the SAMe-TT₂R₂ score to predict warfarin success: Patients with score 0-2 are likely to achieve good TTR; those with score >2 require more intensive monitoring or should be switched to a DOAC 1

Anticoagulation for Venous Thromboembolism

Treatment Duration for VTE

First episode of DVT/PE secondary to transient risk factor: 3 months of anticoagulation 3

First episode of idiopathic (unprovoked) DVT/PE: At least 6-12 months, with consideration for indefinite therapy 3

Two or more episodes of documented DVT/PE: Indefinite anticoagulation 3

First episode with thrombophilia (Factor V Leiden, prothrombin 20210 mutation, antithrombin deficiency, Protein C/S deficiency): 6-12 months with consideration for indefinite therapy 3

First episode with antiphospholipid antibodies or multiple thrombophilic conditions: 12 months recommended, indefinite therapy suggested 3

DOAC vs. Warfarin for VTE

DOACs are first-line agents for treating VTE in eligible patients 4, 5

For VTE with active cancer: Low-molecular-weight heparin remains first-line, though growing evidence supports DOAC use in this population 4

Initial parenteral anticoagulation: Required for 5-10 days before starting dabigatran for VTE treatment 6; rivaroxaban and apixaban can be started immediately without parenteral overlap 4

Cardioversion Management

Elective Cardioversion (AF >48 Hours or Unknown Duration)

Anticoagulation for at least 3 weeks before cardioversion is required using either: 1

• Well-managed VKA (INR 2.0-3.0), OR
• DOAC (dabigatran, rivaroxaban, edoxaban, or apixaban), OR
• TEE-guided approach with abbreviated anticoagulation

After successful cardioversion, continue therapeutic anticoagulation for at least 4 weeks regardless of baseline stroke risk 1

Long-term anticoagulation decisions beyond 4 weeks should be based on CHA₂DS₂-VASc score, not on cardioversion success 1

Urgent Cardioversion (Hemodynamic Instability)

Start therapeutic-dose parenteral anticoagulation before cardioversion if possible, but do not delay emergency intervention 1

After successful urgent cardioversion, continue therapeutic anticoagulation for at least 4 weeks regardless of baseline stroke risk 1

Short-Duration AF (≤48 Hours)

Start anticoagulation at presentation with LMWH or unfractionated heparin at full VTE treatment doses and proceed to cardioversion rather than delaying for 3 weeks 1

Critical Pitfalls to Avoid

Never use aspirin alone or aspirin plus clopidogrel for stroke prevention in AF - they are inferior to oral anticoagulation and are not recommended 1, 2

Do not add antiplatelet therapy to anticoagulation for stroke prevention in AF - this increases bleeding without reducing stroke 1

Do not use bleeding risk scores to withhold anticoagulation - instead, assess and manage modifiable bleeding risk factors 1, 2

Do not reduce DOAC doses unless patients meet specific DOAC-specific criteria to prevent underdosing and avoidable thromboembolic events 1

Do not base anticoagulation decisions on AF pattern (paroxysmal vs. persistent vs. permanent) - stroke risk is the same regardless of pattern 1

Do not switch between DOACs or from DOAC to VKA without clear indication in patients with thromboembolism despite anticoagulation 1

Monitoring and Reassessment

Reassess stroke and bleeding risks at every patient contact to ensure appropriate ongoing anticoagulation 1, 2

DOACs do not require routine laboratory monitoring 5

For warfarin, check INR at least weekly during initiation and at least monthly when stable 1

Modifiable bleeding risk factors must be addressed at each visit including uncontrolled hypertension, concomitant antiplatelet use, excessive alcohol intake, and labile INRs 1, 2