Alteplase, a recombinant tissue plasminogen activator (tPA), is a powerful thrombolytic drug used to treat acute ischemic stroke, which accounts for about 87% of all strokes. An ischemic stroke occurs when a blood clot blocks an artery supplying blood to the brain, leading to the death of brain cells. Alteplase works by converting plasminogen to plasmin, an enzyme that breaks down the fibrin in the clot, thus restoring blood flow to the brain. The effectiveness of this treatment is highly dependent on how quickly it is administered after the onset of stroke symptoms, a concept captured by the phrase, "time is brain".
The Standard 4.5-Hour Treatment Window
For most eligible patients experiencing an acute ischemic stroke, the standard-of-care window for intravenous (IV) alteplase is within 4.5 hours of symptom onset. This window is based on extensive clinical trials, most notably the NINDS trial which established the benefit within 3 hours, and the ECASS III trial which extended this to 4.5 hours for carefully selected patients. However, the benefit of alteplase decreases over time, and earlier treatment is always preferable. Studies have shown that treatment administered within 90 minutes provides a greater benefit compared to treatment between 90 and 180 minutes. The decision to administer alteplase within this timeframe is not automatic. It requires a rapid assessment by a stroke team, including confirming the stroke is ischemic (not hemorrhagic) via brain imaging, usually a non-contrast CT scan, and evaluating the patient against a strict list of inclusion and exclusion criteria.
Extended Time Windows and Advanced Imaging
For specific patient populations, the treatment window for alteplase and other reperfusion therapies has been extended beyond the standard 4.5 hours. This is particularly relevant for:
- Wake-up Strokes: In some cases, a person may wake up with stroke symptoms, making the exact time of onset unknown. Using advanced brain imaging, such as MRI (looking for a DWI-FLAIR mismatch) or CT perfusion imaging, doctors can determine if there is still salvageable brain tissue (the 'penumbra') that can benefit from reperfusion therapy. A positive DWI and negative FLAIR on MRI suggests a recent stroke (within 4.5 hours), making the patient potentially eligible for alteplase, even if the last known well time was much earlier.
- Endovascular Thrombectomy: For patients with a large vessel occlusion (LVO) in the anterior circulation, mechanical thrombectomy can be performed up to 24 hours from symptom onset, based on advanced imaging that shows significant salvageable brain tissue. Many of these patients will first receive alteplase if they are within the 4.5-hour window, in a process known as 'bridging therapy'. The combination has shown better outcomes for some patients. Newer research is even exploring if IV thrombolysis alone can be effective in an extended window (up to 24 hours) for select patients based on perfusion imaging, though more confirmation is needed.
Key Considerations and Risks
While highly effective, alteplase carries risks, with the most significant being symptomatic intracranial hemorrhage (bleeding in the brain). The risk of bleeding must be weighed carefully against the potential benefits of dissolving the clot. Certain conditions significantly increase this risk and serve as contraindications to alteplase, including:
- History of intracranial hemorrhage
- Recent surgery or serious head trauma (within 3 months)
- Active internal bleeding
- Current severe, uncontrolled high blood pressure
- Bleeding disorders
Patient eligibility and risk factors are meticulously reviewed by a healthcare team to ensure the safest and most effective course of treatment.
Comparison of Alteplase vs. Mechanical Thrombectomy
In the modern era of stroke care, alteplase is often used in combination with or as a stepping stone to mechanical thrombectomy for large vessel occlusions. The table below outlines some key differences.
| Feature | Alteplase (IV Thrombolysis) | Mechanical Thrombectomy |
|---|---|---|
| Mechanism | Clot-dissolving medication infused intravenously. | Physical removal of the clot using a stent retriever or aspiration. |
| Primary Indication | Most ischemic strokes, including smaller clots not eligible for thrombectomy. | Large vessel occlusions (LVO) in the anterior circulation. |
| Standard Time Window | Within 4.5 hours of symptom onset. | Within 6 hours of symptom onset for most LVOs. |
| Extended Window | Up to 4.5 hours standard. Up to 24 hours for select patients with appropriate imaging (e.g., DWI/FLAIR mismatch). | Up to 24 hours for select patients with appropriate imaging (e.g., showing salvageable brain tissue). |
| Risk of Hemorrhage | Can increase the risk of intracranial hemorrhage. | Risk of hemorrhage is typically similar or sometimes lower than alteplase alone in large-vessel strokes. |
| Best Practice | First-line therapy for eligible patients, even if thrombectomy is being considered (bridging therapy). | Indicated for LVO strokes regardless of alteplase use, provided eligibility criteria are met. |
Conclusion
In summary, the question of how long after a stroke can you give alteplase is nuanced, with the standard window being 4.5 hours, but extending in specific circumstances. The single most important factor remains the need for rapid medical attention. For the vast majority of patients, the earlier alteplase is administered within the established window, the greater the chance of a positive outcome. The rise of mechanical thrombectomy and advanced imaging techniques has expanded treatment options for select patients with large vessel occlusions, but alteplase remains a cornerstone of early reperfusion therapy. The ultimate goal of every stroke team is to assess the patient, diagnose the type of stroke, and initiate the most appropriate and timely treatment to minimize brain damage and improve functional recovery.
