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Effect of Alteplase on Long-Term Survival After Ischemic Stroke
Among a subset of Third International Stroke Trial participants, alteplase treatment was associated with higher mortality within the first week after stroke and lower mortality afterward.
Numerous randomized trials have assessed thrombolytic therapy for the treatment of acute ischemic stroke. Pooled analyses from these trials indicate that alteplase treatment improves functional outcomes, but the effect on survival remains unclear. Investigators now report the results of long-term follow-up among a subset of participants in the Third International Stroke Trial (IST-3).
Of the 3035 participants in IST-3, 1946 were enrolled in the United Kingdom, Sweden, or Norway, and their vital status after the end of trial participation could be ascertained through national mortality registries. Using these registries, investigators evaluated the association between alteplase treatment and mortality, first during the entirety of follow-up and then during the 0- to 7-day period versus the 8-day to 3-year period after randomization.
During the entire 3-year period of follow-up, the mortality rate was nonsignificantly lower in the alteplase group than in the control group (47% vs. 50%; risk difference, −3.6%; 95% confidence interval, −0.8–8.1%). Mortality was significantly higher in the alteplase group during the first week (10% vs. 7%) but significantly lower among those who survived past the first week (41% vs. 47%). There were no significant differences in these patterns among subgroups defined by age (≤80 years vs. >80), stroke severity (NIH Stroke Scale score ≤10 vs. >10), or time from stroke onset to randomization (≤3 hours vs. 3–6 hours).
This analysis confirms an effect of alteplase treatment suggested by prior trials: Although treatment with alteplase may result in early neurological deterioration or death, it also improves outcomes among the majority of patients who survive the early phase. Overall, any given stroke patient is more likely to benefit than be harmed.
Hooman Kamel, MD reviewing Berge E et al. Lancet Neurol 2016 Sep.
Berge E et al. Effects of alteplase on survival after ischaemic stroke (IST-3): 3 year follow-up of a randomised, controlled, open-label trial. Lancet Neurol 2016 Sep; 15:1028.
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