Role of Tissue Plasminogen Activator in Acute Ischemic Stroke

Objective: To evaluate the literature regarding the use of intravenous tissue plasminogen activator (tPA) in the treatment of acute ischemic stroke, focusing on the appropriate usage criteria and administration time window. Data Sources: A PubMed and MEDLINE search was performed (1990-November 2010) using the key words alteplase, tissue plasminogen activator, thrombolytic, ischemic stroke, and cerebrovascular accident. Study Selection and Data Extraction: Clinical trials published in English were evaluated and relevant primary literature evaluating the use of tPA in acute ischemic stroke was included. Data Synthesis: The NINDS (National Institute of Neurological Disorders and Stroke) trial revealed clinical efficacy of tPA in the treatment of acute ischemic stroke when administered within 3 hours of stroke symptom onset and served as the foundation for the American Heart Association/American Stroke Association (AHA/ASA) acute ischemic stroke guideline recommendations. The ECASS (European Cooperative Acute Stroke Study) I, ECASS II, and ATLANTIS (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke), part A and B, trials each assessed the efficacy of tPA when administered beyond 3 hours of ischemic stroke onset, but the results of each trial did not support its use beyond 3 hours. The ECASS III trial showed clinical efficacy of tPA when administered up to 4.5 hours. The SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) and SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register) registries evaluated the safety and efficacy of tPA at both 3 and 4.5 hours and showed promising results. In 2009, the AHA/ASA stroke guidelines were updated to support the use of tPA in select patients up to 4.5 hours after symptom onset. Conclusions: tPA is effective when administered up to 4.5 hours after ischemic stroke symptom onset in select patients. However, timely administration remains paramount to achievement of optimal therapeutic outcomes.