For a patient with multiple cerebral infarcts and microbleeds, is dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) preferred?

Antiplatelet Therapy for Multiple Cerebral Infarcts with Microbleeds

For patients with multiple cerebral infarcts and microbleeds, single antiplatelet therapy (SAPT) is recommended for long-term secondary stroke prevention, as dual antiplatelet therapy (DAPT) beyond 21-30 days significantly increases intracranial hemorrhage risk without providing additional ischemic stroke protection. 1

Acute Phase Management (First 21-30 Days)

If the patient presents acutely (within 24 hours) with minor stroke or high-risk TIA, short-duration DAPT with aspirin plus clopidogrel for 21-30 days is appropriate despite microbleeds, as the early ischemic risk outweighs hemorrhagic risk during this brief window. 2

• DAPT reduces 90-day recurrent ischemic stroke by 32% when initiated within 24 hours and continued for 21-30 days 2
• The number needed to treat is 92 to prevent one primary outcome event, while the number needed to harm for severe bleeding is 263 1
• This recommendation applies even to patients with microbleeds, as the benefit-risk ratio favors DAPT during the acute phase 2

Long-Term Management (Beyond 30 Days)

After completing the initial 21-30 day DAPT course, transition to single antiplatelet therapy indefinitely. 1, 2

Evidence Against Long-Term DAPT in Microbleed Patients

• Long-term DAPT (>90 days) shows no benefit for recurrent stroke prevention (HR 0.91,95% CI 0.61-1.37) but significantly increases intracranial hemorrhage and major bleeding risk 1
• The exact duration at which hemorrhage risk outweighs benefit is between 21-90 days, with older patients and those with more severe strokes at higher ICH risk 1
• Among patients with ≥5 microbleeds on antiplatelet therapy, 73% of intracranial hemorrhages occurred in this small subset (7.7% of patients), and 82% of these ICH events were disabling or fatal 3

Microbleed Burden Risk Stratification

The presence of microbleeds, particularly ≥5 microbleeds, substantially increases ICH risk but also indicates higher ischemic stroke risk, creating a complex risk-benefit calculation. 3

• Patients with ≥5 microbleeds have an 11.2% 5-year hemorrhage risk on antiplatelet therapy, but also face a 12.0% risk of ischemic events after the first year 3
• During the first year post-stroke, ischemic events exceed hemorrhagic events even in patients with ≥5 microbleeds (11.6% vs 3.9%), but this ratio reverses after one year 3
• Deep microbleeds show stronger association with antiplatelet-related hemorrhage than lobar microbleeds 4

Recommended Long-Term SAPT Options

Choose one of the following single antiplatelet agents: 1, 2

• Clopidogrel 75 mg daily (preferred based on superior efficacy in PAD populations) 1
• Aspirin 81-325 mg daily 1, 2
• Aspirin 50 mg plus extended-release dipyridamole 200 mg twice daily 2

Agent-Specific Considerations for Microbleed Patients

• Aspirin shows stronger association with microbleeds in ICH patients (OR 2.160,95% CI 1.050-4.443) compared to clopidogrel, which showed no significant association 4
• This suggests clopidogrel may be the safer choice for patients with multiple microbleeds requiring long-term antiplatelet therapy 4

Critical Safety Considerations

The following practices increase hemorrhagic risk without benefit and should be avoided: 1, 2

• Never continue DAPT indefinitely - extending beyond 90 days increases major bleeding by 142% (RR 2.42,95% CI 1.37-4.30) without reducing recurrent stroke 2
• Never use triple antiplatelet therapy - the TARDIS trial showed no stroke benefit with significantly increased bleeding 1, 2
• Do not withhold antiplatelet therapy entirely based solely on microbleed presence, as ischemic stroke risk remains substantial and antiplatelet therapy may be safe even with microbleeds 5, 3

Special Clinical Scenarios

For patients requiring endovascular intervention: Short-term DAPT (1-6 months) is reasonable post-procedure even in microbleed patients, as the 12-week symptomatic ICH risk with DAPT was similar between patients with and without microbleeds (4.3% vs 5.5%, P=1.000) 6

For patients with cardioembolic mechanism: Oral anticoagulation is recommended instead of antiplatelet therapy regardless of microbleed status 2

For patients with ≥5 microbleeds beyond one year post-stroke: Consider the heightened long-term hemorrhagic risk (hemorrhage risk matches ischemic risk after one year), and ensure the ongoing indication for antiplatelet therapy remains strong 3

Monitoring Recommendations

• Obtain baseline brain MRI with gradient echo sequences to quantify microbleed burden 4, 6, 3
• Assess leukoaraiosis severity, as it correlates with microbleed number (r=0.42) and may indicate higher hemorrhagic risk 5
• Consider GI protection with proton pump inhibitors for patients at elevated bleeding risk 2