Dual Antiplatelet Therapy After 2 Weeks in Large Vessel Stroke
No, dual antiplatelet therapy (DAPT) should not be initiated after 2 weeks in patients with large vessel stroke, regardless of decreased hemorrhagic transformation risk. DAPT is only indicated for minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) when started within 24-72 hours of symptom onset, and the treatment window for initiating DAPT has already closed by 2 weeks 1, 2.
Why DAPT Cannot Be Started After 2 Weeks
Timing Requirements Are Absolute
DAPT must be initiated within 24-72 hours of symptom onset to provide benefit in stroke prevention 1, 3. The CHANCE trial required initiation within 24 hours, while the more recent INSPIRES trial extended this to 72 hours 3.
The therapeutic window closes rapidly because the benefit of DAPT is concentrated in preventing early recurrent stroke within the first 21 days after the index event 1, 2.
Starting DAPT after 2 weeks provides no additional benefit over single antiplatelet therapy (SAPT) for long-term secondary prevention, as the period of highest early recurrence risk has already passed 1.
Large Stroke Excludes DAPT Regardless of Timing
DAPT is contraindicated in moderate to severe stroke (NIHSS >3) at any time point, including the acute phase 1, 2.
Large vessel strokes typically present with NIHSS scores >3, making them ineligible for DAPT based on stroke severity criteria alone 1.
Aspirin monotherapy was not associated with significant reduction in stroke recurrence among those with severe stroke, and there is no evidence that DAPT would be beneficial in this population 1.
Risk-Benefit Analysis Beyond 21-30 Days
Bleeding Risk Outweighs Benefit
DAPT beyond 90 days is associated with increased major hemorrhage risk (HR 2.32,95% CI 1.10-4.87) without additional stroke prevention benefit 1.
For every 1000 patients treated with DAPT for 90 days, 15 ischemic strokes would be prevented but 5 major hemorrhages would result 1.
The bleeding risk increases significantly with prolonged DAPT duration (HR 2.22-2.32 for >90 days), which is why guidelines explicitly limit DAPT to 21-30 days maximum 1, 2.
Long-Term Intracerebral Hemorrhage Risk
Combining antiplatelets with anticoagulants shows increased intracerebral hemorrhage risk beyond 12 months (OR 1.34,95% CI 1.18-1.53) 4, suggesting that prolonged dual therapy carries cumulative bleeding risk.
Even in the acute phase, most bleeding events (3.1%) occurred within the 21-day DAPT period 5, indicating that extending treatment duration amplifies hemorrhage risk.
Correct Management After 2 Weeks
Single Antiplatelet Therapy Is Indicated
All patients with large vessel stroke should receive SAPT (aspirin 81-325 mg daily or clopidogrel 75 mg daily) indefinitely for long-term secondary prevention 1.
SAPT should be continued long-term regardless of when it was initiated after the acute stroke period 1.
Special Considerations for Anticoagulation
If the large vessel stroke is cardioembolic (e.g., atrial fibrillation), anticoagulation should be initiated within 2 weeks based on stroke severity: mild stroke >3 days, moderate stroke >6-8 days, severe stroke >12-14 days 1.
Anticoagulation timing is guided by stroke size and hemorrhagic transformation risk, not by the 2-week timepoint specifically 1.
Critical Pitfalls to Avoid
Do not confuse the decreased hemorrhagic transformation risk at 2 weeks with an indication to start DAPT - these are unrelated concepts. DAPT timing is determined by the early recurrence risk window, not hemorrhagic transformation risk 1.
Do not extrapolate DAPT benefits from minor stroke trials to large vessel strokes - the evidence base specifically excludes moderate-to-severe strokes (NIHSS >3) 1, 2.
Do not initiate DAPT late in an attempt to provide "catch-up" secondary prevention - the benefit window has closed and only bleeding risk remains 1.