When to start Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) such as apixaban (apixaban), rivaroxaban (rivaroxaban), or dabigatran (dabigatran) in patients with atrial fibrillation (AF) not caused by heart valve problems, deep vein thrombosis (DVT), or pulmonary embolism (PE)?

Indications to Start NOACs

NOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) should be started in patients with nonvalvular atrial fibrillation who have a CHA₂DS₂-VASc score ≥2 in men or ≥3 in women, and NOACs are preferred over warfarin in all NOAC-eligible patients. 1

Primary Indications for NOAC Initiation

Atrial Fibrillation Stroke Prevention

• Start oral anticoagulation when CHA₂DS₂-VASc score reaches threshold: ≥2 for men or ≥3 for women 1
• NOACs are recommended over warfarin except in patients with moderate-to-severe mitral stenosis or mechanical heart valves 1
• The pattern of AF (paroxysmal, persistent, or permanent) does not change the indication—base the decision solely on thromboembolic risk 1

Venous Thromboembolism

• DVT/PE treatment: Start apixaban 10 mg twice daily for 7 days, then 5 mg twice daily 2
• VTE recurrence prevention: After completing at least 6 months of treatment, apixaban 2.5 mg twice daily reduces recurrence risk 2

Post-Orthopedic Surgery Prophylaxis

• Hip or knee replacement: Apixaban 2.5 mg twice daily starting 12-24 hours post-surgery (35 days for hip, 12 days for knee) 2

Absolute Contraindications to NOACs

Do not use NOACs in the following situations:

• Mechanical heart valves 1, 2
• Moderate-to-severe mitral stenosis 1
• Severe renal impairment with CrCl <30 mL/min for rivaroxaban 1 and <15 mL/min for dabigatran 1
• Triple-positive antiphospholipid syndrome (use warfarin instead) 2

NOAC Selection Algorithm

First-Line Choice: Apixaban

Apixaban 5 mg twice daily is the preferred NOAC based on the most favorable safety profile, particularly lower bleeding risk compared to rivaroxaban and dabigatran 3, 4, 5

Dose reduction to 2.5 mg twice daily required if patient has ≥2 of:

• Age ≥80 years 2
• Body weight ≤60 kg 2
• Serum creatinine ≥1.5 mg/dL 2

Alternative NOACs

• Dabigatran 150 mg twice daily: Consider in patients requiring maximum ischemic stroke prevention, as it showed superior efficacy to warfarin 1
• Rivaroxaban 20 mg once daily: May be preferred for patients with adherence concerns due to once-daily dosing, but carries higher bleeding risk than apixaban 4, 5
• Edoxaban: Approved alternative with comparable effectiveness 1

Mandatory Pre-Treatment Assessment

Before initiating any NOAC, evaluate:

• Renal function (creatinine clearance): Required before starting and at least annually thereafter 1, 2
  • In moderate renal impairment (CrCl 30-50 mL/min), assess 2-3 times yearly 1
• Hepatic function: Evaluate before initiation 1
• Bleeding risk using HAS-BLED score: Score ≥3 indicates high bleeding risk requiring closer monitoring 1
• Concomitant medications: Reduce apixaban dose by 50% with combined P-gp and strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) 2

Special Clinical Scenarios

Cardioversion

• AF duration ≥48 hours or unknown: Anticoagulate with NOAC for ≥3 weeks before cardioversion 1
• Continue anticoagulation ≥4 weeks post-cardioversion 1
• Long-term anticoagulation: Continue indefinitely in men with CHA₂DS₂-VASc ≥2 or women with ≥3, regardless of cardioversion success 1

Patients Unsuitable for Warfarin

• Apixaban 5 mg twice daily is superior to aspirin in AF patients deemed unsuitable for warfarin who have ≥1 additional risk factor 1
• Use 2.5 mg twice daily if patient meets ≥2 dose-reduction criteria 1

Critical Safety Monitoring

Perioperative Management

• Discontinue 48 hours before elective surgery with moderate-to-high bleeding risk 2
• Discontinue 24 hours before procedures with low bleeding risk 2
• Restart when adequate hemostasis established—bridging anticoagulation generally not required 2

Neuraxial Anesthesia

• Remove epidural catheter ≥24 hours after last NOAC dose 2
• Wait ≥5 hours after catheter removal before next NOAC dose 2
• Delay 48 hours if traumatic puncture occurs 2

Common Pitfalls to Avoid

• Do not use NOACs in valvular AF: This specifically means moderate-to-severe mitral stenosis or mechanical valves—bioprosthetic valves are acceptable 1
• Do not combine NOACs with antiplatelet therapy long-term: Safety and efficacy not established; limit dual therapy to 1-3 months maximum when required 1
• Do not use INR to monitor NOAC effect: INR measurements are not useful for NOACs except when transitioning to warfarin 2
• Do not assume dose equivalence: Reduced doses are not interchangeable—follow specific criteria for each NOAC 2