“Time is brain” has become the mantra of treatment with IV thrombolysis for acute ischemic stroke patients. Multiple studies have demonstrated better outcomes and safety of IV tissue plasminogen activator (IV tPA) when given sooner after the onset of symptoms. Many of these studies have been of modest size and have included mainly patients at large academic centers, leading some to question the generalizability of these results. Saver and colleagues aimed to examine the relationship between IV tPA administration time and outcomes in a large national dataset in the United States.
The authors used the Get With the Guidelines Stroke registry, which includes 1857 hospitals that contributed data between 2003 and 2012. After excluding patients from sites with missing data and those treated for stroke with methods other than IV tPA, the authors identified 58,353 patients from 1395 sites who were treated after presentation to the emergency department with IV tPA for acute ischemic stroke. The median age of these patients was 72 years, and just over half were women. The mean onset to treatment time was 144 min; a total of 9.3% were treated within 90 min, 77.2% between 91 and 180 min, and 13.6% between 181 and 270 min. The most common factors associated with earlier treatment included more severe initial National Institutes of Health Stroke Scale score, arrival to the hospital via ambulance, and arrival during daylight/weekday hours.
In the entire cohort examined, 8.8% of patients died in the hospital, there was a 4.9% intracranial hemorrhage rate, independent ambulation was achieved at discharge in 33.4%, and 38.6% were discharged to home. For every 15-min earlier interval of tPA administration there was a significantly reduced in-hospital mortality, a decreased rate of intracerebral hemorrhage, more frequent independent ambulation at discharge, and a higher rate of discharge to home.
Compared with those patients treated between 181 and 270 min, those treated within the first 90 min had significantly lower in-hospital mortality [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.64–0.86], decreased rates of symptomatic intracranial hemorrhage (OR, 0.72; 95% CI, 0.60–0.87), increased frequency of independent ambulation at discharge (OR, 1.51; 95% CI, 1.35–1.69), and higher likelihood to be discharged to home (OR, 1.33; 95% CI, 1.20–1.46). For every 1000 patients treated, every 15-min reduction in time to treatment was associated with 18 more patients with improved ambulation at discharge, 13 additional patients discharged to a more independent environment, and 4 fewer in-hospital deaths.
This remarkable study proves what many clinicians caring for acute stroke patients have always believed—the faster we can give tPA, the better the outcomes. This is a very large study that included patients in diverse settings nationally, including community-based hospitals. IV tPA remains the standard of care of acute ischemic stroke patients presenting within established time windows without contraindications, and hospitals should continue to concentrate on system-based improvements that will allow the drug to be given even faster in the face of these encouraging results.
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