Alteplase for stroke: Time, but not age or severity, affects outcomes

Counter to current guidelines in some countries where it is used, intravenous alteplase has been shown to be effective in stroke patients irrespective of age up to 4.5 hours after stroke onset, according to a study published online Aug. 6 in The Lancet. However, for best outcomes, speed was important.

In a meta-analysis of the results of nine trials utilizing alteplase, first author Jonathan Emberson, PhD, of the University of Oxford in the U.K., and colleagues explored outcomes in patients relative to age, time to needle and severity of stroke.

Many countries limit use of alteplase based on these three variables: in Europe, for example, while alteplase can be administered to patients up to 4.5 hours following stroke onset, recommendations and regulations caution against use in severe or mild stroke and restricts use to patients 80 years old or younger. In the U.S., alteplase may be used only within three hours of stroke onset, may be used for severe and mild stroke and has no age restrictions for use.

Emberson et al found that 31 percent of patients observed achieved a good stroke outcome on the modified Rankin scale (0 to 1) at three to six months, with earlier use achieving higher benefits. Good outcome odds for patients given alteplase within three hours of onset was 1.75; patients given alteplase between three and 4.5 hours saw good outcome odds ratio of 1.26; and after 4.5 hours the odds of a good outcome were 1.15.

Alteplase had no affect at 6.3 hours and beyond.

Age of the patient and severity of stroke did not change odds when treatment delays were taken into consideration, nor did age affect the length of time physicians had to implement treatment with alteplase.

They noted that symptomatic intracranial hemorrhage risk increased with use of alteplase. Type 2 parenchymal hemorrhage occurred in 6.8 percent of patients treated with alteplase as opposed to 1.3 percent of patients who received a control treatment. In 2.7 percent of alteplase patents, fatal type 2 parenchymal hemorrhage occurred within seven days, as opposed to 0.4 percent of control patients. No other increased risk of death was seen.

However, they found that beyond the initial treatment period, patients had an average absolute increase in good survival by the three to six month mark for about 10 percent of patients treated within three hours and 5 percent of patients treated in less than 4.5 hours. Again, these findings were irrespective of age or stroke severity.

In an editorial, Michael D Hill, MD, MSc, of the University of Calgary in Canada, and colleagues commented that European license labels for altephase are obsolete compared with the outcomes of this study. They added that, as the real key seems to be time, based on these findings, “Benchmark for treatment times should be revised audited and enforced.”

They suggested that a median 30-minute door-to-needle time might be a better target, as the shortened guideline time would encourage faster treatment and provide more patients the chance to succeed in recovery.

Emberson et al wrote that they will be exploring independent effects of other variables on outcomes such as blood pressure, sex and baseline imaging features.