Editors' note: Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window

Abstract

In their recent meta-analysis of 4 randomized-controlled trials (RCTs) evaluating the safety and efficacy of IV alteplase for patients treated beyond 4.5 hours after last known well, Dr. Tsivgoulis et al. confirm each trial's reported advantage of treatment over placebo. Although the risk-to-benefit ratio of IV alteplase undoubtedly dwindles with time—as prior trials and meta-analyses have demonstrated—there is a population of slow—or perhaps, slower—progressors who may yet benefit from treatment in the extended treatment window. Important to note is the 4 included RCTs from this meta-analysis restricted patient inclusion based on the presence of a reversible ischemic lesion, as identified via perfusion CT or diffusion-weighted MRI. Among patients who meet these imaging and other clinical criteria, the risk of symptomatic hemorrhage following thrombolysis is considerable (adjusted odds ratio 6.22, 95% confidence interval 1.37–28.26), and yet the long-term outcomes demonstrate a clear functional benefit without a higher probability of mortality. In response, Dr. Ishida cautions readers that these data do not indicate a shift in the paradigm of acute treatment for all-comers. Instead, they should be used to extend treatment opportunities for historically ineligible patients. What's more is that we should not use these data to justify treatment delays or to curtail stroke education emphasizing rapid evaluation and triage for stroke-like symptoms. Time is still tissue, although it may be more or less tissue on the individual patient level. In their recent meta-analysis of 4 randomized-controlled trials (RCTs) evaluating the safety and efficacy of IV alteplase for patients treated beyond 4.5 hours after last known well, Dr. Tsivgoulis et al. confirm each trial's reported advantage of treatment over placebo. Although the risk-to-benefit ratio of IV alteplase undoubtedly dwindles with time—as prior trials and meta-analyses have demonstrated—there is a population of slow—or perhaps, slower—progressors who may yet benefit from treatment in the extended treatment window. Important to note is the 4 included RCTs from this meta-analysis restricted patient inclusion based on the presence of a reversible ischemic lesion, as identified via perfusion CT or diffusion-weighted MRI. Among patients who meet these imaging and other clinical criteria, the risk of symptomatic hemorrhage following thrombolysis is considerable (adjusted odds ratio 6.22, 95% confidence interval 1.37–28.26), and yet the long-term outcomes demonstrate a clear functional benefit without a higher probability of mortality. In response, Dr. Ishida cautions readers that these data do not indicate a shift in the paradigm of acute treatment for all-comers. Instead, they should be used to extend treatment opportunities for historically ineligible patients. What's more is that we should not use these data to justify treatment delays or to curtail stroke education emphasizing rapid evaluation and triage for stroke-like symptoms. Time is still tissue, although it may be more or less tissue on the individual patient level.