Although current therapy for acute ischemic stroke remains limited to intravenous recombinant tissue plasminogen activator (tPA) administered within 3 hours of symptom onset, other treatment options are on the horizon.
Here we discuss recent and ongoing research that may:
- Broaden the criteria for thrombolysis with tPA so that more patients with stroke can benefit from treatment.
- Extend the 3-hour window in select patients.
- Expand the armamentarium to include more effective thrombolytic agents, alternative means of delivery of thrombolytics, mechanical approaches to clot lysis, neuroprotective therapies, and combination thrombolytic/neuroprotective therapies.
CURRENT THERAPY: tPA AND THE 3-HOUR WINDOW
In 1996, the FDA approved the use of intravenous tPA for acute ischemic stroke. This was a landmark in the history of stroke treatment; before that time, thrombolytic therapy was not recommended for patients with stroke.
The approval of tPA was based primarily on the results of the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Study, in which 624 patients with ischemic stroke received placebo or tPA within 3 hours of symptom onset. Approximately 50% of study participants were treated within 90 minutes of stroke onset.1 Initiation of tPA therapy within 90 minutes was associated with an odds ratio of 2.83 for a favorable outcome (95% confidence interval [CI], 1.77 to 4.53); if therapy was started between 90 and 180 minutes after symptom onset, the odds ratio was 1.53 (95% CI, 1.11 to 2.11).2
The patients who had received tPA had a 30% greater probability of recovering with little or no deficit after 3 months, as assessed by multiple outcome measures. The benefits associated with tPA treatment were maintained at 1 year.3
Patients who were most likely to have an excellent outcome were those younger than 75 years and those who had a mild to moderate stroke (as indicated by a score of less than 20 on the National Institutes of Health Stroke Scale [NIHSS], which is available at www.strokecenter.org/trials/scales/ nihss.pdf.). Nonetheless, tPA treatment improved the likelihood of a favorable outcome in patients with severe stroke (NIHSS score greater than 20) and in older patients.1
The major risk associated with tPA treatment was symptomatic intracerebral hemorrhage (ICH), which occurred in 6.4% of patients who received tPA but in only 0.6% of those in the placebo group. However, there was no significant difference in mortality at 3 months (17% of patients who received tPA and 20% of those who received placebo) or at 1 year (24% and 28%, respectively).1,3
Since the NINDS study results were published, several other groups have reported similar efficacy and safety data for tPA treatment. Despite this strong evidence, only 2% to 4% of all stroke patients currently receive tPA.4 The major impediment to use of tPA is the late arrival of many stroke patients at the emergency department for evaluation and treatment. Thus, it is important to teach patients about the signs and symptoms of stroke so they know when to seek medical care.