An acute ischemic stroke (AIS) occurs when a blood clot blocks a blood vessel supplying the brain, leading to a rapid deprivation of oxygen and nutrients. The adage “time is brain” perfectly captures the urgency of this medical emergency, as every minute of untreated stroke leads to the loss of millions of neurons. Fortunately, the U.S. Food and Drug Administration (FDA) has approved several therapies designed to restore blood flow, a process known as reperfusion, and minimize damage.
Intravenous Thrombolytic Therapy: The Clot-Busters
Thrombolytic agents, or “clot-busters,” are a cornerstone of acute ischemic stroke treatment. These medications are administered intravenously (IV) to dissolve the clot obstructing blood flow. Prompt administration is critical and hinges on a confirmed diagnosis of AIS, typically by ruling out a hemorrhagic stroke with a non-contrast head CT scan.
Alteplase (Activase)
For decades, alteplase was the only FDA-approved pharmacologic treatment for AIS. This recombinant tissue plasminogen activator (tPA) works by initiating a biochemical reaction that breaks down the fibrin within the blood clot.
- Administration: Alteplase is given via a two-part IV infusion. A small portion of the dose is given as an initial bolus, followed by the remaining dose over one hour.
- Time Window: To maximize benefit and minimize risk, alteplase should be administered as soon as possible after symptom onset. While the FDA-approved window is within 3 hours, guidelines may extend this to 4.5 hours in specific eligible patients.
Tenecteplase (TNKase)
A major advancement in pharmacotherapy for stroke occurred in March 2025, when the FDA approved tenecteplase for the treatment of AIS. Tenecteplase is a genetically engineered variant of alteplase with several key advantages.
- Administration: A notable benefit is its simpler and faster administration. Tenecteplase is given as a single, five-second IV bolus, which can help streamline workflows in emergency settings where every second is crucial.
- Clinical Evidence: Based on the results of the AcT trial, tenecteplase was shown to be non-inferior to alteplase in terms of safety and efficacy, paving the way for its approval.
- Potential Bleeding Risk: As with alteplase, the most significant risk associated with tenecteplase is bleeding, particularly intracranial hemorrhage. A careful risk-benefit assessment is performed for each patient.
Endovascular Thrombectomy: Mechanical Clot Removal
For patients with a stroke caused by a large vessel occlusion, particularly in the internal carotid or middle cerebral arteries, endovascular thrombectomy (EVT) is a highly effective treatment. This procedure is often performed in combination with IV thrombolysis.
- Procedure: During EVT, a neurointerventionalist uses a long, thin tube called a catheter, inserted through an artery in the groin, to reach the blocked vessel in the brain. A stent retriever device, or aspiration system, is then used to remove the clot mechanically.
- FDA Clearance: The FDA has cleared multiple devices for this procedure, enabling physicians to select the best tool for the specific case. The first mechanical device, the MERCI retriever, was cleared in 2004, with improved stent-retriever devices following later.
- Time Window Expansion: Research has significantly expanded the time window for EVT. For carefully selected patients, imaging can help identify salvageable brain tissue (the penumbra), allowing for treatment up to 24 hours after symptom onset.
Complementary and Supportive Acute Stroke Management
Successful stroke management involves more than just reperfusion therapies. Comprehensive care in a specialized stroke center improves outcomes by managing patient physiology and preventing complications. Key supportive measures include:
- Blood Pressure Management: Maintaining appropriate blood pressure is vital. Very high pressure can increase the risk of bleeding, while very low pressure can reduce perfusion to the brain.
- Glucose and Fever Control: Controlling blood sugar levels and fever is important, as both can worsen brain injury.
- Deep Vein Thrombosis Prophylaxis: Stroke patients are at an increased risk of blood clots in the legs. Prophylaxis, including compression devices, is used to prevent deep vein thrombosis and pulmonary embolism.
- Rehabilitation Planning: While not an acute therapy, early planning for rehabilitation—which may include speech, physical, and occupational therapy—begins in the hospital.
A Comparison of Thrombolytics for Acute Ischemic Stroke
| Feature | Alteplase (Activase) | Tenecteplase (TNKase) |
|---|---|---|
| Mechanism | Recombinant tissue plasminogen activator (tPA) | Genetically engineered tPA variant with higher fibrin specificity |
| Administration | Intravenous (IV) infusion over one hour | Single, five-second IV bolus |
| Time Window | Within 4.5 hours of symptom onset for eligible patients | Primarily within 3-4.5 hours, but being studied in extended windows |
| Convenience | Requires a more complex, longer administration process | Offers faster, simpler administration, which may reduce delays |
| Efficacy | Established efficacy for timely use in AIS | Proven non-inferior to alteplase in clinical trials |
| FDA Approval | 1996 | March 2025 |
Conclusion
The landscape of acute ischemic stroke treatment has evolved significantly, moving from a single pharmacological option to a combination of cutting-edge therapies. The FDA-approved approach now involves a dual strategy: intravenous thrombolysis using alteplase or the newer, faster-acting tenecteplase, complemented by endovascular thrombectomy for large vessel occlusions. Speed is paramount, and the integration of these medical and procedural interventions, guided by advanced imaging and expertise in a specialized center, is critical for achieving the best outcomes and reducing long-term disability for stroke patients. A rapid, coordinated response remains the most powerful tool in the fight against stroke.
Mayo Clinic is a leading source for patient information on stroke diagnosis and treatment, including details on approved therapies.
