Continued extension of time for thrombolysis in stroke

Background: Current guidelines for ischemic stroke recommend the time to thrombolysis be within 4.5 hours after onset of stroke. Guidelines are based on noncontrasted CT, but CT perfusion and perfusion-diffusion MRI may show salvageable brain tissue beyond the 4.5 hours. Studies have shown better outcomes in patients who were chosen for reperfusion based on tissue viability rather than time from onset of stroke. This has resulted in a disparity between the time windows used for thrombolysis.

Study design: Multicenter, randomized, placebo-controlled trial.

Setting: Hospitalized patients with acute ischemic stroke from 16 centers in Australia, 10 centers in Taiwan, 1 center in New Zealand, and 1 center in Finland.

Synopsis: 225 patients (aged 18 years and older) with acute ischemic stroke with hypoperfused but salvageable areas of brain detected on CT perfusion imaging or perfusion-diffusion MRI were randomly assigned to receive IV alteplase or placebo between 4.5 and 9 hours after onset of stroke or on awakening with stroke. Primary outcome measured on modified Rankin scale was 0 (no neurologic deficit) or 1. Before the trial was fully enrolled, it was terminated because of a loss of equipoise based on positive results from a previous trial. Of the patients enrolled, the primary outcome occurred in 35.4% of the alteplase group and 29.5% in the placebo group (adjusted risk ratio, 1.44). Symptomatic intracerebral hemorrhage was experienced in 6.2% of the patients in the alteplase group and 0.9% of patients in the placebo group (adjusted risk ratio, 7.22).

Not all centers may have access to perfusion imaging, so the study’s findings may not be applicable to multiple sites.

Bottom line: Diffusion-perfusion imaging may be useful in determining salvageable brain tissue in acute ischemic stroke that may benefit from thrombolysis after the standard 4.5-hour window, but further studies need to be conducted before guidelines are changed.

Citation: Ma H et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380(19):1795-803.

Dr. Rogers is a hospitalist at Ochsner Health System, New Orleans.

Background: Current guidelines for ischemic stroke recommend the time to thrombolysis be within 4.5 hours after onset of stroke. Guidelines are based on noncontrasted CT, but CT perfusion and perfusion-diffusion MRI may show salvageable brain tissue beyond the 4.5 hours. Studies have shown better outcomes in patients who were chosen for reperfusion based on tissue viability rather than time from onset of stroke. This has resulted in a disparity between the time windows used for thrombolysis.

Study design: Multicenter, randomized, placebo-controlled trial.

Setting: Hospitalized patients with acute ischemic stroke from 16 centers in Australia, 10 centers in Taiwan, 1 center in New Zealand, and 1 center in Finland.

Synopsis: 225 patients (aged 18 years and older) with acute ischemic stroke with hypoperfused but salvageable areas of brain detected on CT perfusion imaging or perfusion-diffusion MRI were randomly assigned to receive IV alteplase or placebo between 4.5 and 9 hours after onset of stroke or on awakening with stroke. Primary outcome measured on modified Rankin scale was 0 (no neurologic deficit) or 1. Before the trial was fully enrolled, it was terminated because of a loss of equipoise based on positive results from a previous trial. Of the patients enrolled, the primary outcome occurred in 35.4% of the alteplase group and 29.5% in the placebo group (adjusted risk ratio, 1.44). Symptomatic intracerebral hemorrhage was experienced in 6.2% of the patients in the alteplase group and 0.9% of patients in the placebo group (adjusted risk ratio, 7.22).

Not all centers may have access to perfusion imaging, so the study’s findings may not be applicable to multiple sites.

Bottom line: Diffusion-perfusion imaging may be useful in determining salvageable brain tissue in acute ischemic stroke that may benefit from thrombolysis after the standard 4.5-hour window, but further studies need to be conducted before guidelines are changed.

Citation: Ma H et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380(19):1795-803.

Dr. Rogers is a hospitalist at Ochsner Health System, New Orleans.

Background: Current guidelines for ischemic stroke recommend the time to thrombolysis be within 4.5 hours after onset of stroke. Guidelines are based on noncontrasted CT, but CT perfusion and perfusion-diffusion MRI may show salvageable brain tissue beyond the 4.5 hours. Studies have shown better outcomes in patients who were chosen for reperfusion based on tissue viability rather than time from onset of stroke. This has resulted in a disparity between the time windows used for thrombolysis.

Study design: Multicenter, randomized, placebo-controlled trial.

Setting: Hospitalized patients with acute ischemic stroke from 16 centers in Australia, 10 centers in Taiwan, 1 center in New Zealand, and 1 center in Finland.

Synopsis: 225 patients (aged 18 years and older) with acute ischemic stroke with hypoperfused but salvageable areas of brain detected on CT perfusion imaging or perfusion-diffusion MRI were randomly assigned to receive IV alteplase or placebo between 4.5 and 9 hours after onset of stroke or on awakening with stroke. Primary outcome measured on modified Rankin scale was 0 (no neurologic deficit) or 1. Before the trial was fully enrolled, it was terminated because of a loss of equipoise based on positive results from a previous trial. Of the patients enrolled, the primary outcome occurred in 35.4% of the alteplase group and 29.5% in the placebo group (adjusted risk ratio, 1.44). Symptomatic intracerebral hemorrhage was experienced in 6.2% of the patients in the alteplase group and 0.9% of patients in the placebo group (adjusted risk ratio, 7.22).

Not all centers may have access to perfusion imaging, so the study’s findings may not be applicable to multiple sites.

Bottom line: Diffusion-perfusion imaging may be useful in determining salvageable brain tissue in acute ischemic stroke that may benefit from thrombolysis after the standard 4.5-hour window, but further studies need to be conducted before guidelines are changed.

Citation: Ma H et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380(19):1795-803.

Dr. Rogers is a hospitalist at Ochsner Health System, New Orleans.