What is the appropriate time range for using Tissue Plasminogen Activator (tPA) (Alteplase)?

From the Guidelines

Tissue Plasminogen Activator (tPA) (Alteplase) should be administered within 3 to 4.5 hours of ischemic stroke symptom onset, with the most benefit occurring when given as early as possible, ideally within the first 3 hours. The standard dose is 0.9 mg/kg, with a maximum dose of 90 mg over 60 minutes, and an initial 10% of the dose given as a bolus over 1 minute 1. This time-dependent efficacy of tPA reflects the pathophysiology of ischemic stroke, where earlier reperfusion salvages more brain tissue and improves outcomes.

Key Considerations

• The American Heart Association/American Stroke Association recommends tPA administration within 3 hours of symptom onset for selected patients, with equal recommendation for patients <80 and >80 years of age 1.
• For patients who can be treated between 3 and 4.5 hours of symptom onset, tPA is recommended for those ≤80 years of age, without a history of both diabetes mellitus and prior stroke, NIHSS score ≤25, not taking any oral anticoagulants, and without imaging evidence of ischemic injury involving more than one-third of the MCA territory 1.
• Treatment should be initiated as quickly as possible within the above-listed time frames because time to treatment is strongly associated with outcomes 1.

Patient Eligibility

• Patients should be screened for eligibility criteria, including blood pressure, blood glucose, CT findings, prior antiplatelet therapy, and end-stage renal disease 1.
• IV tPA is recommended in patients whose BP can be lowered safely (to <185/110 mm Hg) with antihypertensive agents, with the physician assessing the stability of the BP before starting IV tPA 1.
• IV tPA is recommended in otherwise eligible patients with initial glucose levels >50 mg/dL 1.

Administration

• The dose of tPA should be administered as an initial 10% bolus over 1 minute, followed by the remaining 90% infused over 60 minutes 1.
• tPA should be used in settings where cardiac and neurological monitoring is available and where complications can be managed promptly.

From the Research

Time Range for Using Tissue Plasminogen Activator (tPA) (Alteplase)

• The appropriate time range for using Tissue Plasminogen Activator (tPA) (Alteplase) is within 4.5 hours of symptom onset, as supported by multiple studies 2, 3, 4, 5, 6.
• This time frame is consistently mentioned across the studies as the window for effective treatment with tPA (Alteplase) or its alternative, tenecteplase, for patients with acute ischemic stroke.
• The studies compared the efficacy and safety of tenecteplase with alteplase, with results indicating that tenecteplase is a viable alternative to alteplase within this 4.5-hour time frame 2, 3, 4, 5, 6.
• The evidence suggests that treatment with tPA (Alteplase) or tenecteplase within 4.5 hours of symptom onset can lead to improved functional outcomes and reduced disability in patients with acute ischemic stroke 2, 3, 4, 5, 6.

Key Findings

• The ORIGINAL study found that tenecteplase was noninferior to alteplase in patients with acute ischemic stroke within 4.5 hours of symptom onset 2.
• A systematic review and meta-analysis found that tenecteplase was associated with higher likelihood of excellent functional outcome and reduced disability at 3 months compared to alteplase 4.
• A comparative effectiveness study found similar effectiveness and safety outcomes with tenecteplase compared to alteplase in patients with acute ischemic stroke 5.
• The AcT trial found that intravenous tenecteplase was a reasonable alternative to alteplase for patients with acute ischemic stroke who meet standard criteria for thrombolysis 6.