When should dual antiplatelet therapy (DAPT) be initiated instead of single antiplatelet therapy in stroke patients in the Intensive Care Unit (ICU)?

Dual Antiplatelet Therapy in ICU Stroke Patients

Initiate dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel in ICU stroke patients who have minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) within 24 hours of symptom onset, continuing for exactly 21 days before transitioning to single antiplatelet therapy. 1

Specific Criteria for DAPT vs Single Antiplatelet

Use DAPT (Aspirin + Clopidogrel) When:

• Minor stroke with NIHSS ≤3 or high-risk TIA with ABCD2 score ≥4 1
• Non-cardioembolic stroke mechanism (patients requiring anticoagulation should not receive DAPT) 1
• Symptom onset within 72 hours (ideally within 12-24 hours, though benefit extends to 72 hours) 1, 2
• Intracranial hemorrhage excluded on neuroimaging before initiation 1
• Not receiving thrombolysis, or if thrombolysis given, wait 24 hours post-alteplase with repeat imaging excluding hemorrhage 1

Use Single Antiplatelet (Aspirin Alone) When:

• Moderate-to-severe stroke with NIHSS >3 3
• Low-risk TIA with ABCD2 score <4 3
• Presentation >24 hours after symptom onset (though recent evidence supports DAPT up to 72 hours, guidelines emphasize the 24-hour window) 1
• High bleeding risk including history of gastrointestinal hemorrhage, coagulopathy, or concurrent anticoagulation 3
• Urgent carotid endarterectomy planned (to reduce perioperative bleeding risk) 1

Dosing Protocol for DAPT

Loading Doses:

• Aspirin: 160-325 mg (single dose on day 1) 1, 4
• Clopidogrel: 300-600 mg (300 mg based on CHANCE trial, 600 mg based on POINT trial) 1, 4

Maintenance Doses:

• Aspirin: 81 mg daily (days 2-21) 1
• Clopidogrel: 75 mg daily (days 2-21) 1

Duration:

• DAPT for exactly 21 days (maximum 30 days), then transition to single antiplatelet therapy indefinitely 1, 3, 5
• The benefit of DAPT is confined to the first 21 days; prolonged duration increases bleeding risk without additional benefit 1, 5

Alternative DAPT Regimen (Aspirin + Ticagrelor)

For mild-moderate stroke (NIHSS ≤5) or high-risk TIA (ABCD2 ≥4): 1

Loading Doses:

• Aspirin: 300-325 mg 1
• Ticagrelor: 180 mg 1

Maintenance:

• Aspirin: 75-100 mg daily 1
• Ticagrelor: 90 mg twice daily for 30 days 1

Critical Timing Considerations

• Initiate DAPT as early as possible, ideally within 12 hours of symptom onset 1
• Maximum benefit when started within 24 hours, though efficacy extends to 72 hours 6, 2
• Recent evidence from the INSPIRES trial demonstrates consistent benefit when DAPT initiated within 72 hours (HR 0.70 for 48-72 hour window) 6, 2
• Start DAPT before discharge from ED/ICU to ensure compliance 1

Safety Profile and Bleeding Risk

• Absolute increase in major hemorrhage: 0.5% (from 0.4% to 0.9%) with DAPT 1
• Number needed to treat: 67 patients to prevent one ischemic stroke 1
• Number needed to harm: 200 patients to cause one major hemorrhage 1
• For every 1000 patients treated with DAPT for 21 days, 15 ischemic strokes are prevented but 5 major hemorrhages occur 1
• Consider GI protection with proton pump inhibitors in patients at higher risk of gastrointestinal bleeding 1, 3

Common Pitfalls to Avoid

• Do not continue DAPT beyond 21-30 days - bleeding risk increases significantly (HR 2.22-2.32) without additional benefit after 90 days 1, 3, 5
• Do not use DAPT in moderate-to-severe stroke (NIHSS >3) - no proven benefit and increased bleeding risk 3
• Do not delay aspirin loading beyond 48 hours in patients not eligible for DAPT - benefit is time-dependent 4
• Do not use DAPT as substitute for thrombolysis or thrombectomy in eligible patients 4
• Counsel patients explicitly that DAPT is temporary (21 days only) and they must transition to single antiplatelet therapy 1

Special Populations in ICU

Dysphagia:

• Rectal aspirin 325 mg daily or aspirin 81 mg daily via enteral tube plus clopidogrel 75 mg daily via enteral tube 1

Post-Thrombolysis:

• Delay antiplatelet initiation until 24 hours post-alteplase with repeat imaging excluding hemorrhage 1