From the Guidelines
Tissue plasminogen activator (tPA) remains the best initial treatment for acute ischemic stroke, particularly when administered within 4.5 hours of symptom onset, as it improves functional outcomes and reduces long-term morbidity 1. The decision to use tPA depends on several factors, including time since symptom onset, stroke severity, and presence of contraindications such as recent surgery, active bleeding, anticoagulant use, or uncontrolled hypertension. Key considerations for tPA administration include:
- Confirming the diagnosis with neuroimaging to exclude hemorrhage
- Checking blood glucose levels
- Assessing for contraindications
- Administering the medication as soon as possible, with the goal of minimizing onset-to-treatment times, which is a key driver of efficacy for tPA 1. While tPA carries a risk of symptomatic intracranial hemorrhage, this risk is outweighed by the benefit of improved functional outcomes when administered within the appropriate time window 1. For optimal stroke management, rapid assessment and treatment initiation are crucial, as "time is brain" with approximately 1.9 million neurons lost per minute of untreated stroke. In patients with large vessel occlusions, mechanical thrombectomy may be considered as a complementary or alternative treatment, particularly when presented within 24 hours of symptom onset. The efficacy of tPA stems from its ability to convert plasminogen to plasmin, which breaks down fibrin clots, and its use is associated with improved outcomes for a broad spectrum of patients who can be treated within 3 hours of the last known well time before symptom onset and a mildly more selective spectrum of patients who can be treated between 3 and 4.5 hours of the last known well time 1.
From the Research
Current Status of TPA in Acute Ischemic Stroke Treatment
- Tissue plasminogen activator (TPA) remains the only approved systemic reperfusion therapy suitable for most patients presenting timely with acute ischemic stroke 2.
- The use of TPA has been supported by accumulating real-world experience for over 20 years regarding its safety and effectiveness 2.
- TPA is still considered the standard of care in the treatment of patients with acute ischemic stroke, despite ongoing controversies within the broader medical community 3.
Advances and Future Directions
- Novel strategies for rapid patient assessment and the potential for mobile stroke units (MSU) that shorten onset-to-needle time and increase TPA treatment rates are being explored 2.
- The use of TPA in the era of non-vitamin K antagonist oral anticoagulants (NOACs) is highlighted, and its continuing role in large vessel occlusion (LVO) patients eligible for mechanical thrombectomy (MT) is discussed 2.
- Research is ongoing to develop "tPA helpers" that may reduce the incidence of intracranial hemorrhage (ICH) and hemorrhagic transformation (HT) after TPA treatment, potentially enabling clinicians to extend therapeutic time and increase the probability of excellent outcomes 4.
Challenges and Limitations
- Despite its proven efficacy, TPA remains substantially underutilized due to challenges such as narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, and perceived lack of efficacy in certain high-risk subgroups 5.
- The need for better education and consensus among both the medical and lay public is necessary to optimize the use of TPA for all eligible stroke patients 5.
- Ongoing and future research should continue to improve upon the efficacy of TPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion 5.