What is the recommended anticoagulation therapy for patients with non-valvular atrial fibrillation (AF) at high risk of stroke?

Risk of Stroke in Non-Valvular Atrial Fibrillation

For patients with non-valvular atrial fibrillation at high risk of stroke (CHA₂DS₂-VASc score ≥2), oral anticoagulation with a direct oral anticoagulant (DOAC) such as apixaban, dabigatran, rivaroxaban, or edoxaban is strongly recommended over warfarin, aspirin, or no therapy. 1

Risk Stratification Using CHA₂DS₂-VASc Score

The CHA₂DS₂-VASc scoring system is the recommended tool for assessing stroke risk in non-valvular AF patients. 1 This score assigns points for the following risk factors:

• Congestive heart failure: 1 point 1
• Hypertension: 1 point 1
• Age ≥75 years: 2 points 1
• Diabetes mellitus: 1 point 1
• Prior stroke/TIA/thromboembolism: 2 points 1
• Vascular disease: 1 point 1
• Age 65-74 years: 1 point 1
• Sex category (female): 1 point 1

The annual stroke risk increases approximately 2% for each 1-point increase in CHA₂DS₂-VASc score, ranging from 1.9% with a score of 0 to 18.2% with a score of 6. 1

Anticoagulation Recommendations Based on Risk Level

Low Risk (CHA₂DS₂-VASc = 0 in males, 1 in females)

• No antithrombotic therapy is reasonable 1, 2
• If the score is 1 in a female due to sex alone, this represents truly low risk and no therapy is needed 2

Intermediate Risk (CHA₂DS₂-VASc = 1 in males)

• Oral anticoagulation with a DOAC is strongly recommended over aspirin or no therapy 2
• No antithrombotic therapy or aspirin may be considered as alternatives, but oral anticoagulation is preferred 1

High Risk (CHA₂DS₂-VASc ≥2)

• Oral anticoagulation is mandatory 1, 2
• DOACs are preferred over warfarin 1, 2
• Options include: apixaban 5 mg twice daily, dabigatran 150 mg twice daily, rivaroxaban, or edoxaban 1, 3
• Patients with prior stroke or TIA have approximately 12% annual stroke risk and require immediate anticoagulation 4

Choice of Anticoagulant: DOACs vs. Warfarin

DOACs are strongly recommended over warfarin for eligible patients with non-valvular AF. 1, 2 The evidence supporting this preference includes:

• Lower risk of intracranial hemorrhage compared to warfarin 2, 5
• Similar or superior efficacy in stroke prevention 5
• No requirement for routine INR monitoring 2
• More predictable pharmacokinetics and fewer drug-food interactions 5

Specific DOAC Dosing

Apixaban: 5 mg twice daily; reduce to 2.5 mg twice daily if patient has at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 3

Dabigatran: 150 mg twice daily is preferred for high stroke risk due to superior efficacy compared to warfarin 1, 2

When Warfarin is Required

Warfarin (target INR 2.0-3.0) remains the anticoagulant of choice for: 1, 6, 2

• Mechanical heart valves
• Moderate-to-severe mitral stenosis
• End-stage chronic kidney disease (CrCl <15 mL/min) or hemodialysis 1

INR should be checked at least weekly during warfarin initiation and monthly when stable. 1, 6

Critical Evidence: Why Aspirin is NOT Recommended

Antiplatelet therapy alone (aspirin or aspirin plus clopidogrel) is strongly recommended AGAINST for stroke prevention in AF, regardless of stroke risk. 1, 2 The evidence is clear:

• Oral anticoagulation reduces stroke risk by 62%, while aspirin provides only 22% risk reduction 2, 4
• Aspirin does not reduce bleeding risk compared to anticoagulation 7
• Dual antiplatelet therapy (aspirin plus clopidogrel) increases bleeding risk without adequate stroke protection 1, 2

Special Populations and Dose Adjustments

Chronic Kidney Disease

• For moderate-to-severe CKD with CHA₂DS₂-VASc ≥2, reduced doses of DOACs may be considered, but safety data are limited 1
• Dabigatran and rivaroxaban are NOT recommended in end-stage CKD or dialysis due to lack of clinical trial evidence 1
• Warfarin (INR 2.0-3.0) is reasonable for end-stage CKD or hemodialysis patients 1
• Evaluate renal function before initiating DOACs and reassess at least annually 1

Patients Unable to Maintain Therapeutic INR

• If time in therapeutic range (TTR) is <65-70% on warfarin, switch to a DOAC 1, 2

Common Pitfalls to Avoid

Do not use bleeding risk as a reason to withhold anticoagulation. 2 Instead:

• Use the HAS-BLED score to identify modifiable bleeding risk factors (uncontrolled hypertension, labile INRs, alcohol excess, concomitant NSAIDs/aspirin) 1, 2
• A high HAS-BLED score (≥3) indicates need for more frequent monitoring and aggressive management of modifiable factors, not avoidance of anticoagulation 2

Do not continue aspirin after initiating oral anticoagulation. 2 The combination increases bleeding risk without providing additional stroke prevention benefit. 2

Do not discontinue anticoagulation after cardioversion or ablation if stroke risk factors persist. 2 The CHA₂DS₂-VASc score determines long-term anticoagulation need, not the AF pattern (paroxysmal, persistent, or permanent). 1

Do not arbitrarily reduce DOAC doses. 2 Use only manufacturer-specified dose reduction criteria; arbitrary reductions lead to inadequate stroke prevention. 2

Real-World Anticoagulation Gaps

Despite strong guideline recommendations, fewer than 33% of high-risk NVAF patients receive oral anticoagulation within 60 days of diagnosis, and only 53% receive it within 2 years. 8 The most common barriers include:

• Patient refusal to monitoring (37.3%) 7
• Perceived high bleeding risk (31.1%) 7
• Uncontrolled hypertension (27.9%) 7
• Frequent falls (27.6%) 7

About 20% of Spanish NVAF patients who should receive anticoagulation are instead treated with antiplatelet agents, which do not reduce stroke risk adequately. 7 Most of these patients do not have clear contraindications to oral anticoagulation, particularly with DOACs available. 7