After holding aspirin and clopidogrel for 1–2 days following thrombolysis for an ischemic stroke in a patient previously on these agents for a TIA, should the antiplatelet regimen be restarted with a loading dose?

Restarting Antiplatelet Therapy After Brief Hold Post-Thrombolysis

No loading dose is required when restarting aspirin and clopidogrel after a 1–2 day hold following thrombolysis—simply resume maintenance dosing (aspirin 75–100 mg daily plus clopidogrel 75 mg daily) without additional loading. 1, 2

Clinical Context and Rationale

Your patient was already loaded and on therapeutic dual antiplatelet therapy (DAPT) for the TIA when the stroke occurred. The brief 1–2 day interruption for thrombolysis does not eliminate the antiplatelet effect sufficiently to warrant re-loading:

• Clopidogrel's active metabolite has a platelet-binding half-life of approximately 7 days, meaning significant residual platelet inhibition persists even after 24–48 hours of drug cessation. 3
• A European Society of Cardiology case series explicitly demonstrates this principle: when a patient on ticagrelor developed stroke post-PCI, received thrombolysis with antiplatelets held, and was switched to clopidogrel the next day, no loading dose was administered—only maintenance clopidogrel 75 mg daily was started. 1

Restart Protocol After Thrombolysis

Timing of restart:

• Wait until 24 hours post-thrombolysis and confirm no intracranial hemorrhage on repeat neuroimaging before restarting any antiplatelet agents. 1, 2

Dosing when restarting (no loading required):

• Clopidogrel 75 mg once daily (maintenance dose only). 1, 2
• Aspirin 75–100 mg once daily (maintenance dose only). 1, 2

Duration of DAPT:

• Continue dual therapy for a total of 21 days from the original TIA event (not 21 days from the stroke), then transition to single antiplatelet therapy indefinitely. 1, 2

Why Loading Doses Are Not Needed Here

Loading doses serve a specific purpose—rapid platelet inhibition in treatment-naïve patients:

• Standard clopidogrel 75 mg daily requires approximately 5 days to achieve maximal platelet inhibition, which is why loading doses (300–600 mg) are used in acute settings. 2, 4
• Your patient already received loading doses for the TIA and was on therapeutic DAPT when the stroke occurred. 1
• After only 1–2 days off therapy, residual antiplatelet effect remains, and re-loading would unnecessarily increase bleeding risk without additional benefit. 1

Evidence Supporting Maintenance-Only Restart

The ESC case-based guideline provides direct precedent:

• A post-PCI patient on ticagrelor developed stroke on day 3, received IV thrombolysis with antiplatelets held, and was switched to clopidogrel on day 4 without a loading dose (75 mg daily only), with aspirin discontinued. 1
• The Task Force commentary explicitly states: "The switch from ticagrelor to clopidogrel following stroke was achieved without administering a clopidogrel loading dose." 1

Canadian Stroke Best Practice Guidelines support this approach:

• For patients already on clopidogrel who undergo procedures or interruptions: "Continue clopidogrel 75 mg daily without an additional loading dose." 1

Critical Safety Considerations

Do not re-load because:

• Re-loading after only 1–2 days off therapy provides no additional platelet inhibition benefit but significantly increases hemorrhagic risk, particularly in the immediate post-thrombolysis period. 1, 2
• The patient's stroke occurred while already on DAPT, suggesting the mechanism was likely not inadequate antiplatelet effect but rather the underlying high-risk vascular pathology. 1

Monitor for bleeding complications:

• The combination of recent thrombolysis plus DAPT restart carries inherent bleeding risk (moderate-to-severe bleeding occurs in approximately 0.9% of DAPT patients vs 0.4% on aspirin alone). 1, 5
• Consider GI protection with a proton pump inhibitor given the patient's recent thrombolysis and resumption of DAPT. 1

Common Pitfall to Avoid

Do not treat this as a new acute event requiring loading doses. The patient was already therapeutically anticoagulated when the stroke occurred, and the brief hold for thrombolysis does not reset the clock. Re-loading would be analogous to giving a second loading dose to a patient already on maintenance therapy—unnecessary and potentially harmful. 1, 2