Tissue Plasminogen Activator and Time to Treatment

Tissue Plasminogen Activator and Time to Treatment The National Institute of Neurological Disorders and Stroke studies, published in 1995, demonstrated for the first time that in patients selected by clinical and noncontrast computed tomography criteria, intravenous TPA (IV tissue plasminogen activator) resulted in improved outcomes compared with standard treatment. Since that time, safe and quick delivery of IV TPA has become the primary focus of acute stroke management and forever changed the way that acute stroke care is delivered. The most important variable that predicts response to treatment is time from symptom onset to treatment initiation. On the basis of European Cooperative Acute Stroke Study III (ECASS III), treatment with IV TPA in Europe is approved out to 4.5 hours, but the benefit of treatment if started >3 hours is marginal if any. IV TPA is not approved >3 hours in the United States and best results occur if treatment is started within 2 hours. The number needed to treat of 3.1 within 3 hours is probably ≈2 if treatment is started within 2 hours. Recently, this lesson has been reinforced by the International Stroke Trial (IST), which once again confirmed that time is the most important determination of IV TPA benefit, and that other criteria, such as advanced age and increased stroke severity, commonly used to exclude patients from treatment, do not in fact preclude benefit. Although such a narrow time window necessarily limits treatment to only a subset of stroke patients, such is the reality of reperfusion therapy at least with IV TPA as demonstrated now by abundant human clinical trial data. Because IV TPA was approved in 1996, this critical importance of time to treatment has generated a massive change in the way stroke is managed by prehospital emergency medical services (EMS) and emergency departments (EDs). Guidelines have promoted triage of all acute stroke patients to the nearest primary stroke center (PSC). More than 800 PSCs have been certified throughout the country. PSCs often enlarge their ability to treat more patients by promoting treatment at outlying support hospitals using either telemedicine or drip and ship transfer agreements. These important developments have resulted in a gradual increase in the percent of patients treated with IV TPA. Although it is difficult to be certain of this proportion, it is probably still <10% nationwide. In Houston, Texas where strong community and EMS education programs have existed since the development of IV TPA treatment for stroke, and where there is a citywide collaboration to report treatment rates and complications, in the last quarter of 2011, the treatment rate was 9% of all strokes directly taken to citywide stroke center EDs (81% of those patients eligible were treated).