What are the recommendations for using Direct Oral Anticoagulants (DOACs) in patients with Atrial Fibrillation (AF) who have experienced a Cerebrovascular Accident (CVA) with infarct and have a history of Intracranial (IC) bleeding?

Management of DOACs in AF After CVA with Infarct and History of Intracranial Bleeding

DOACs can be cautiously restarted 10-14 days after an ischemic stroke with infarct in AF patients, but a prior history of spontaneous intracranial hemorrhage constitutes a contraindication to anticoagulation unless the underlying cause has been definitively reversed. 1

Critical Decision Point: Prior ICH vs. Acute Stroke with Hemorrhagic Transformation

The management hinges on distinguishing between:

• Prior spontaneous intracranial hemorrhage (absolute contraindication)
• Hemorrhagic transformation of current ischemic stroke (relative contraindication with timing considerations)

If Prior Spontaneous ICH History:

• Anticoagulation is contraindicated according to both DOAC labeling and VKA guidelines unless the cause of ICH has been reversed 1
• Specific contraindication exists for cerebral amyloid angiopathy, where recurrent ICH risk is extremely high and generally precludes anticoagulation use 1
• Non-pharmacological alternatives should be prioritized, including catheter ablation or left atrial appendage occlusion as potential substitutes for stroke prevention 1
• If anticoagulation must be restarted due to very high cardioembolic risk and low estimated recurrent ICH risk, this may be considered at 10-14 days, but this represents off-label use with substantial risk 1

If Current Ischemic Stroke with Hemorrhagic Transformation:

Timing of DOAC initiation follows the "1-3-6-12 day rule" based on infarct size: 1

• TIA (no infarct on imaging): Start DOAC after 1 day 1
• Small, non-disabling infarct: Start DOAC after 3 days 1
• Moderate stroke: Start DOAC after 6 days 1
• Large infarcts involving large arterial territory: Delay DOAC for 12-14 days (or even 3 weeks) 1

Evidence-Based Timing Recommendations

• The ACC recommends initiating oral anticoagulation when considered safe from hemorrhagic transformation perspective, typically between 2 and 14 days following an acute ischemic event 1
• Research data support that early DOAC introduction (1-3 days) may be safe in carefully selected patients with small- and medium-sized cardioembolic strokes, with large infarct size being the only independent predictor of post-DOAC intracranial bleeding 2
• Pre-DOAC CT imaging at 24-36 hours after stroke onset is essential to assess for hemorrhagic transformation before initiating anticoagulation 2

DOAC Selection When Anticoagulation is Appropriate

DOACs are strongly preferred over warfarin when anticoagulation is deemed appropriate: 1

• DOACs demonstrate 50% reduction in intracranial hemorrhage risk compared to warfarin 1, 3, 4
• Among DOACs, dabigatran 110 mg presents the lowest ICH risk (SUCRA 87.3), with 53% lower relative risk compared to rivaroxaban 20 mg 3
• Apixaban demonstrates the lowest gastrointestinal bleeding risk among all DOACs, though ICH rates are similar across DOACs 5
• The 2024 ESC Guidelines recommend DOACs in preference to VKAs for all eligible AF patients except those with mechanical heart valves or moderate-to-severe mitral stenosis 1

Mandatory Pre-Treatment Assessment

Before initiating any DOAC: 1, 6, 7

• Assess renal function - DOACs are contraindicated in severe renal impairment (CrCl <30 mL/min for most agents) 6, 7
• Evaluate for dose reduction criteria - Do not underdose unless specific criteria are met (age ≥80 years, body weight ≤60 kg, serum creatinine ≥133 μmol/L for apixaban) 1
• Screen for triple-positive antiphospholipid syndrome - DOACs are not recommended and VKAs should be used instead due to increased thrombotic event rates 6, 7
• Exclude prosthetic heart valves - DOACs are not recommended in patients with prosthetic valves, particularly after TAVR where higher death and bleeding rates were observed 6, 7

Critical Pitfalls to Avoid

• Never use bleeding risk scores to withhold anticoagulation - These should guide management of modifiable risk factors, not decisions to start or stop anticoagulation 1
• Do not add antiplatelet therapy to anticoagulation for stroke prevention in AF, as this increases bleeding without reducing thromboembolism 1
• Avoid inappropriate dose reduction of DOACs unless patients meet specific criteria, as underdosing leads to inadequate stroke prevention 1
• Do not switch between DOACs or from DOAC to VKA without clear indication in patients with embolic stroke on adequate anticoagulation 1

Monitoring After DOAC Initiation

• Follow-up imaging at 7 days after DOAC initiation is recommended to assess for delayed hemorrhagic transformation 2
• If neurological deterioration occurs, urgent imaging and consideration of DOAC reversal with specific agents (idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors) may be necessary 8
• Interrupting anticoagulation is mandatory if active bleeding occurs until the cause is identified and resolved 1