Fifteen minutes sooner, four in 1,000 more lives saved. That appears to be the benefit ratio for timely reperfusion of patients who present with acute ischemic stroke, according to results published June 19 in JAMA.
Clinical trials and an analysis of pooled data from studies that looked at time to therapy and treatment benefits with intravenous tissue-type plasminogen activator (t-PA) have pointed to improved outcomes with reperfusion within 4.5 hours of onset. Earlier treatment seemed to be associated with greater benefit, but those studies had moderate to small study samples that limited generalizability.
Jeffrey L. Saver, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues addressed that shortcoming by using data from the Get With the Guidelines-Stroke national registry. Based on entries between 2003 and 2012, they identified 58,353 patients from 1,395 sites who were treated at hospital emergency departments with intravenous tPA within 4.5 hours. They categorized treatment by onset to treatment time—0 to 90 minutes, 91 to 180 minutes and 181 to 270 minutes—and compared time intervals to outcomes.
Overall, the mean onset to time for intravenous tPA treatment was 144 minutes; 9.3 percent received reperfusion between 0 to 90 minutes; 77.2 percent between 91 to 180 minutes; and 143.6 between 181 to 270 minutes.
The mortality for the whole group was 8.8 percent. Another 4.9 percent had intracranial hemorrhage, 33.4 percent had independent ambulation at discharge and 38.6 percent were discharged to home. There was an association between earlier treatment and all outcomes. Every 15-minute increment of earlier treatment lowered the odds on an adverse outcome such as death and increased the odds of a good outcome such as discharge to home.
Patients in the 0-to-90-minute group were less likely to die or have intracranial hemorrhage and more likely to independently ambulate or be discharged to a more independent place than those in the 81-to-270-minute group. The findings were consistent across subgroups.
On a number needed to treat basis, Saver et al calculated that for every 1,000 treated patients, a 15-minute faster treatment resulted in:
- 18 more patients with improved ambulation at discharge;
- Eight more patients with fully independent ambulation;
- 13 more patients discharged to a more independent environment;
- Seven more discharged to home; and
- Four fewer dying before discharge.
“[E]very 15-minute acceleration in start of tPA after onset was associated with patients having a 4 percent greater odds of walking independently at discharge, a 3 percent greater odds of being discharged to home rather than an institution, a 4 percent lower odds of death before discharge, and a 4 percent lower odds of experiencing symptomatic hemorrhagic transformation of infarct,” they wrote.
The results add weight to efforts to shorten “door-to-needle” time for initiating tPA treatment in acute ischemic stroke patients and to streamline the process for acute stroke care, Saver et al proposed.
The analysis included a large and diverse patient population and a spectrum of types of hospitals that allowed the researchers to expand on previous studies. Nonetheless, unmeasured confounders could bias results, and the outcomes studied were short-term only.