What anticoagulation therapy is recommended for an adult patient with a history of atrial fibrillation or deep vein thrombosis, who is not currently taking warfarin?

Anticoagulation for Atrial Fibrillation or Deep Vein Thrombosis (Not on Warfarin)

Direct oral anticoagulants (DOACs)—specifically apixaban, rivaroxaban, dabigatran, or edoxaban—are the first-line anticoagulation therapy for patients with atrial fibrillation or venous thromboembolism who are not currently taking warfarin. 1, 2

For Atrial Fibrillation

Risk Stratification and Indication

• Calculate the CHA₂DS₂-VASc score to determine stroke risk 1
• Anticoagulation is mandatory for men with CHA₂DS₂-VASc ≥2 or women with CHA₂DS₂-VASc ≥3 1
• Any patient with prior stroke or TIA requires anticoagulation regardless of score 3

First-Line DOAC Selection

DOACs are recommended over warfarin for all eligible patients with non-valvular atrial fibrillation (Class 1, Level of Evidence: A). 1, 2 The evidence demonstrates DOACs are at least non-inferior and often superior to warfarin for stroke prevention, with significantly lower rates of intracranial hemorrhage 1, 2

Among DOACs, apixaban demonstrates the most favorable bleeding profile with a hazard ratio of 0.69 (95% CI 0.60-0.80) for major bleeding compared to warfarin 2, 4

Specific DOAC Dosing for AF:

• Apixaban: 5 mg orally twice daily (or 2.5 mg twice daily if patient has ≥2 of: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) 1, 3, 4
• Rivaroxaban: 20 mg orally once daily with food (15 mg daily if CrCl 30-50 mL/min) 1, 5
• Dabigatran: 150 mg orally twice daily 1
• Edoxaban: 60 mg orally once daily 1

When Warfarin is Mandatory

Warfarin remains the only option for patients with mechanical heart valves or moderate-to-severe mitral stenosis, with target INR 2.0-3.0 1, 2, 3

Critical Pitfall to Avoid

Never use aspirin alone or aspirin plus clopidogrel as stroke prevention in AF—this combination is inferior to oral anticoagulation for stroke prevention with similar bleeding rates. 2 A high HAS-BLED score (≥3) should prompt correction of modifiable bleeding risk factors but rarely justifies withholding anticoagulation when stroke risk is present 2, 6

For Deep Vein Thrombosis/Venous Thromboembolism

First-Line DOAC Selection

DOACs are first-line therapy for VTE treatment in eligible patients. 1, 6 The dosing differs from AF and requires specific initiation regimens:

Specific DOAC Dosing for VTE:

• Apixaban: 10 mg orally twice daily for first 7 days, then 5 mg orally twice daily 1
• Rivaroxaban: 15 mg orally twice daily with food for first 21 days, then 20 mg daily with food 1
• Dabigatran: 150 mg orally twice daily when preceded by 5-10 days of parenteral anticoagulation 1
• Edoxaban: 60 mg orally once daily when preceded by at least 5-10 days of parenteral anticoagulation 1

Note the critical difference: Apixaban and rivaroxaban have built-in initiation doses and do not require parenteral lead-in therapy, whereas dabigatran and edoxaban require at least 5 days of parenteral anticoagulation (LMWH, unfractionated heparin, or fondaparinux) before starting 1

Extended VTE Prevention (After 6 Months)

After completing 6 months of initial VTE therapy, reduced-dose options can be considered for secondary prevention 1:

• Apixaban: 2.5 mg orally twice daily 1
• Rivaroxaban: 10 mg orally daily 1

Cancer-Associated VTE

For patients with cancer-associated VTE, DOACs are preferred over both LMWH and warfarin due to better compliance and ease of use. 1 However, patients with gastrointestinal and genitourinary malignancies may have higher bleeding risk with DOACs 1

Alternative options for cancer-associated VTE include:

• Dalteparin: 200 units/kg subcutaneously once daily for 1 month, then 150 IU/kg subcutaneously once daily (months 2-6) 1
• Enoxaparin: 1 mg/kg twice daily or 1.5 mg/kg once daily, subcutaneously 1

Monitoring Requirements

For DOACs:

• Assess renal function at baseline and at least annually (more frequently if CrCl 30-60 mL/min or age >75 years) 2, 3
• Periodic reassessment of bleeding risk and stroke risk 1, 3
• No routine INR monitoring required 1

For Warfarin (if used):

• INR monitoring weekly during initiation 1
• INR monitoring monthly once stable in therapeutic range (INR 2.0-3.0) 1
• Target time in therapeutic range (TTR) ≥70%; if TTR remains <70% despite optimization, switch to a DOAC 2

Common Clinical Pitfalls

The most dangerous error is withholding anticoagulation based on bleeding risk scores alone—this denies patients the substantial mortality and morbidity benefits of stroke prevention 2, 3

Never underdose DOACs based solely on bleeding concerns—this increases stroke risk without proven safety benefit 2, 3

Elderly patients (≥75 years) have both higher bleeding and higher stroke risk, but the net clinical benefit of anticoagulation remains strongly positive in this population. 2, 3

For VTE dosing, ensure you use VTE-specific doses, not AF doses—for example, rivaroxaban for VTE maintenance should be 20 mg daily, not 15 mg daily as used in some AF trials 1