Intravenous Tissue Plasminogen Activator for Stroke
Intravenous Tissue Plasminogen Activator for Stroke
Background: Intravenous tissue plasminogen activator (IV tPA) is currently approved by the Food and Drug Administration for use in acute ischemic stroke patients up to 3 h from symptom onset, based primarily on the National Institute of Neurological Disorders and Stroke tPA trials published in 1995. The most recent trial published with IV tPA in stroke (European Cooperative Acute Stroke Study [ECASS] III) studied patients between 3 and 4.5 h from symptom onset and found a benefit to treatment in the rate of favorable outcome when compared to placebo, with no difference in mortality. Objectives: To examine the patient selection criteria and primary outcomes in ECASS III as compared to prior clinical trials and the current practice in the United States to determine how these new data could be applied to clinical practice. Discussion: With the exception of the longer time from symptom onset to treatment, ECASS III used more restrictive patient selection criteria than is the current practice in the United States to determine patient eligibility for IV tPA. Conclusions: Based on the combined data from all trials, the benefits of thrombolysis with IV tPA for acute ischemic stroke outweigh the risks of treatment for selected patients up to 4.5 h from symptom onset. It is already known that thrombolysis is not beneficial for all stroke patients and strict criteria should be applied before treatment. As time from symptom onset increases, the need for careful patient selection likely also increases.
The only treatment approved in the United States by the Food and Drug Administration (FDA) for acute ischemic stroke is thrombolysis with intravenous recombinant tissue plasminogen activator (IV tPA) within 3 h of symptom onset. Individual centers report an IV tPA treatment rate between 3.0% and 8.5% of all stroke admissions. However, using data from the country as a whole, estimates are that the actual rate of IV tPA use in the United States is 1.8% to 2.1% of all ischemic stroke patients. The primary reason patients are not treated is due to the short (3 h) window of opportunity. Although thrombolysis has the potential to significantly improve outcomes by facilitating reperfusion of brain tissue before irreversible brain injury occurs, its use is accompanied by the possibility for symptomatic intracerebral hemorrhage causing increased disability or death. As the duration of brain ischemia increases, the concern is that there is an increased risk of tPA-associated hemorrhage into the ischemic core, as well as a decreased likelihood of clinical benefit from reperfusion of irreversibly damaged brain. A recently published trial showed a benefit to treatment with IV tPA in patients treated 3–4.5 h from symptom onset. This review will summarize the inclusion criteria and results from the randomized trials with IV tPA for stroke and discuss implications for treatment decisions.
Abstract and Introduction
Abstract
Background: Intravenous tissue plasminogen activator (IV tPA) is currently approved by the Food and Drug Administration for use in acute ischemic stroke patients up to 3 h from symptom onset, based primarily on the National Institute of Neurological Disorders and Stroke tPA trials published in 1995. The most recent trial published with IV tPA in stroke (European Cooperative Acute Stroke Study [ECASS] III) studied patients between 3 and 4.5 h from symptom onset and found a benefit to treatment in the rate of favorable outcome when compared to placebo, with no difference in mortality. Objectives: To examine the patient selection criteria and primary outcomes in ECASS III as compared to prior clinical trials and the current practice in the United States to determine how these new data could be applied to clinical practice. Discussion: With the exception of the longer time from symptom onset to treatment, ECASS III used more restrictive patient selection criteria than is the current practice in the United States to determine patient eligibility for IV tPA. Conclusions: Based on the combined data from all trials, the benefits of thrombolysis with IV tPA for acute ischemic stroke outweigh the risks of treatment for selected patients up to 4.5 h from symptom onset. It is already known that thrombolysis is not beneficial for all stroke patients and strict criteria should be applied before treatment. As time from symptom onset increases, the need for careful patient selection likely also increases.
Introduction
The only treatment approved in the United States by the Food and Drug Administration (FDA) for acute ischemic stroke is thrombolysis with intravenous recombinant tissue plasminogen activator (IV tPA) within 3 h of symptom onset. Individual centers report an IV tPA treatment rate between 3.0% and 8.5% of all stroke admissions. However, using data from the country as a whole, estimates are that the actual rate of IV tPA use in the United States is 1.8% to 2.1% of all ischemic stroke patients. The primary reason patients are not treated is due to the short (3 h) window of opportunity. Although thrombolysis has the potential to significantly improve outcomes by facilitating reperfusion of brain tissue before irreversible brain injury occurs, its use is accompanied by the possibility for symptomatic intracerebral hemorrhage causing increased disability or death. As the duration of brain ischemia increases, the concern is that there is an increased risk of tPA-associated hemorrhage into the ischemic core, as well as a decreased likelihood of clinical benefit from reperfusion of irreversibly damaged brain. A recently published trial showed a benefit to treatment with IV tPA in patients treated 3–4.5 h from symptom onset. This review will summarize the inclusion criteria and results from the randomized trials with IV tPA for stroke and discuss implications for treatment decisions.
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