First-Line Treatment for Non-Valvular Atrial Fibrillation
Direct oral anticoagulants (DOACs)—specifically apixaban, dabigatran, rivaroxaban, or edoxaban—are the first-line treatment for stroke prevention in patients with non-valvular atrial fibrillation who have elevated thromboembolic risk (CHA₂DS₂-VASc score ≥2 in men or ≥3 in women). 1, 2, 3
Risk Stratification Determines Treatment
Calculate the CHA₂DS₂-VASc score to determine stroke risk: Congestive heart failure (1 point), Hypertension (1 point), Age ≥75 years (2 points), Diabetes (1 point), prior Stroke/TIA/thromboembolism (2 points), Vascular disease (1 point), Age 65-74 years (1 point), and female Sex (1 point). 1, 3
For CHA₂DS₂-VASc ≥2 (men) or ≥3 (women): Initiate oral anticoagulation—DOACs are preferred over warfarin. 1, 3
For CHA₂DS₂-VASc = 1 (men) or 2 (women): Consider oral anticoagulation based on individual bleeding risk and patient preference, though evidence remains equivocal in this intermediate-risk population. 1
For CHA₂DS₂-VASc = 0 (men) or 1 (women, with only sex as risk factor): No anticoagulation is recommended. 1
Why DOACs Are Preferred Over Warfarin
DOACs reduce intracranial hemorrhage risk by 56-60% compared to warfarin while maintaining equivalent or superior efficacy for stroke prevention. 2, 4
Dabigatran 150 mg twice daily demonstrated superiority to warfarin (1.1% vs 1.7% stroke rate, HR 0.66, p<0.001) with lower intracranial hemorrhage rates (0.3% vs 0.7%). 1
Apixaban 5 mg twice daily showed superiority to warfarin (1.3% vs 1.6% stroke rate, HR 0.79, p<0.001) with significantly lower major bleeding (2.1% vs 3.1%) and intracranial hemorrhage (0.2% vs 0.5%). 1
Rivaroxaban 20 mg daily was non-inferior to warfarin (2.1% vs 2.4% stroke rate, HR 0.88) with similar major bleeding but lower intracranial hemorrhage (0.5% vs 0.7%). 1
DOACs require no routine coagulation monitoring, have fixed dosing, fewer drug-drug interactions, and more predictable pharmacokinetics than warfarin. 5, 6
Specific DOAC Dosing and Renal Considerations
Renal function is critical for DOAC selection and dosing:
Dabigatran 150 mg twice daily for CrCl >30 mL/min; consider 75 mg twice daily for CrCl 15-30 mL/min (though safety/efficacy unestablished); contraindicated if CrCl <15 mL/min. 1
Apixaban 5 mg twice daily is standard; reduce to 2.5 mg twice daily if patient has ≥2 of: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Rivaroxaban should not be used if CrCl <15 mL/min. 1
When Warfarin Remains an Option
Warfarin (target INR 2.0-3.0) is an acceptable alternative when DOACs are contraindicated, not tolerated, or patient preference dictates, but requires meticulous INR monitoring with time in therapeutic range (TTR) >70% for optimal efficacy and safety. 1
Aspirin Is NOT First-Line Treatment
Aspirin alone should NOT be used for stroke prevention in atrial fibrillation—it provides only 19% stroke risk reduction compared to 64% with oral anticoagulation, without significantly better safety. 2
Aspirin is recommended only for patients who absolutely cannot take any oral anticoagulant due to contraindications or refusal. 1, 2
The combination of aspirin plus clopidogrel offers more protection than aspirin alone but increases major bleeding risk and remains inferior to oral anticoagulation. 1, 2
Critical Pitfalls to Avoid
Never discontinue anticoagulation based on rhythm status—stroke risk is determined by CHA₂DS₂-VASc score, not whether the patient is currently in atrial fibrillation or sinus rhythm. 7, 3
Do not use aspirin as "bridging therapy" while waiting to start anticoagulation after ischemic stroke—it increases symptomatic intracranial hemorrhage without preventing recurrent ischemic events. 2
Avoid combining DOACs with antiplatelet agents unless there is a separate compelling indication (e.g., recent coronary stenting), as safety and efficacy of this combination are not established. 1
Monitor renal function regularly (at least annually, more frequently if CrCl <60 mL/min) as declining renal function necessitates DOAC dose adjustment or discontinuation. 1, 5