Dual Antiplatelet Therapy After Thrombolysis for MI
Yes, dual antiplatelet therapy (DAPT) should be initiated in patients who have undergone thrombolysis for myocardial infarction, and this should be started as soon as possible after fibrinolytic therapy is administered. 1, 2
Evidence-Based Recommendation
DAPT with aspirin plus a P2Y12 inhibitor is recommended for all patients with acute coronary syndromes, including those who receive fibrinolytic therapy. 1 The most recent 2025 ACC/AHA/ACEP/NAEMSP/SCAI guidelines explicitly state that dual antiplatelet therapy is recommended for patients with ACS, and this applies regardless of whether they undergo PCI or receive thrombolysis. 1
Specific Regimen After Thrombolysis
Aspirin: Should be administered at 162 mg daily in combination with thrombolytic therapy and continued long-term at 75-100 mg daily. 2
P2Y12 Inhibitor: Clopidogrel 75 mg once daily (without a loading dose) should be started immediately and continued for at least 28 days, and ideally up to 12 months. 2
No loading dose of clopidogrel is used in the post-fibrinolysis setting, which is a critical distinction from PCI patients. 1, 2
Supporting Evidence from Major Trials
The COMMIT trial specifically evaluated this exact scenario in 45,852 STEMI patients who received fibrinolytic therapy. 2 Patients were randomized to receive clopidogrel 75 mg daily (no loading dose) or placebo, both in combination with aspirin 162 mg daily, starting within 24 hours of symptom onset. 2 The results demonstrated:
- 9% relative risk reduction in the composite of re-infarction, stroke, or death (p=0.002). 2
- 7% relative risk reduction in death from any cause (p=0.029). 2
- No significant excess of major bleeding (0.58% vs 0.55%, p=0.59), even in patients aged ≥70 years or those who received fibrinolytic therapy. 2
The CLARITY trial confirmed similar benefits when clopidogrel was added to aspirin in STEMI patients receiving fibrinolysis within 12-24 hours of symptom onset. 1
Duration of Therapy
DAPT should be continued for at least 12 months as the default strategy in patients with ACS who are not at high bleeding risk. 1 This applies to both fibrinolysis-treated and PCI-treated patients. 1
For patients at high bleeding risk, shorter durations (3-6 months) may be reasonable, but the minimum duration should still be at least 1 month. 1, 3
Safety Considerations
The remarkable safety profile of DAPT after fibrinolysis in COMMIT was attributed to three key factors: 1, 2
- No loading dose of clopidogrel (unlike PCI patients who receive 300-600 mg loading)
- Uniform use of low-dose aspirin (162 mg, not 325 mg)
- Careful patient selection excluding those with high bleeding risk
Common Pitfalls to Avoid
Do not withhold DAPT due to concerns about bleeding after thrombolysis—the COMMIT trial definitively showed this combination is safe. 2
Do not use a clopidogrel loading dose in the immediate post-fibrinolysis period, as this was not studied and may increase bleeding risk. 1, 2
Do not discontinue both antiplatelet agents simultaneously if bleeding occurs—maintain at least aspirin if possible, as stopping both agents dramatically increases thrombotic risk. 4, 5
Do not delay P2Y12 inhibitor initiation—it should be started as soon as possible after fibrinolysis, ideally within the first 24 hours. 1, 2
Alternative P2Y12 Inhibitors
While clopidogrel has the strongest evidence base in the fibrinolysis setting, ticagrelor may be considered as an alternative, though it should be initiated after the acute phase (typically >24 hours post-fibrinolysis). 1, 6 A meta-analysis showed similar bleeding and ischemic outcomes when switching to ticagrelor versus continuing clopidogrel after fibrinolysis. 6
Prasugrel should be avoided in fibrinolysis-treated patients due to lack of safety data in this population and increased bleeding risk. 3
If Urgent Surgery Is Required
If the patient requires urgent surgery within days of receiving DAPT after thrombolysis, aspirin should be continued perioperatively if bleeding risk allows, and the P2Y12 inhibitor should be restarted as soon as possible postoperatively (within 48 hours ideally). 1, 4