HONOLULU – , based on a review of more than 40,000 U.S. stroke patients.
Current U.S. stroke management guidelines say that thrombolytic therapy with tissue plasminogen activator (tPA; alteplase; Activase) is contraindicated for index stroke patients who had a prior stroke within the previous 3 months (Stroke. 2018 Mar;). But analysis of 293 U.S. patients who received thrombolytic treatment for an index acute ischemic stroke despite having had a recent, prior stroke showed no increased risk for adverse outcomes when the prior stroke occurred more than 30 days before, , said at the International Stroke Conference sponsored by the American Heart Association.
“The risk of symptomatic intracranial hemorrhage [ICH] after thrombolysis was highest among those with a history of prior ischemic stroke within the past 14 days,” said Dr. Shah, a neurologist at Duke University in Durham, N.C.
“Even after many adjustments we still saw a high risk of symptomatic ICH within the first 2 weeks, suggesting that these patients are at especially high risk” from treatment with tissue plasminogen activator for the index stroke. These findings “are very important because I don’t see a randomized trial happening to test the hypothesis,” Dr. Shah said in an interview.
He also suggested that prior treatment with tPA was not an important factor, just the occurrence of a recent, prior ischemic stoke that left blood vessels in the affected brain region “friable and at high risk for hemorrhage,” he said.
Hisused data from 40,396 patients with an acute ischemic stroke who presented at and received treatment with tPA at any of 1,522 hospitals that participated in the Get With the Guidelines-Stroke program during 2009-2015. The analysis focused on 30,655 of these patients with no prior stroke history who served as the controls, and 293 who had a prior ischemic stroke within the preceding 90 days. These 293 patients further broke into 43 who received thrombolysis within 14 days of their prior stroke, 47 who had the treatment 15-30 days after their prior stroke, and 203 who underwent thrombolysis 31-90 days after their prior stroke. Patients ages’ in both the no-stroke history and recent-stroke subgroups each averaged 80 years.
A comparison between all 293 patients who had a prior stroke within 90 days and the controls showed no statistically significant difference in the rate of symptomatic ICH: 5% among those with no stroke history and 8% in those with a recent stroke. There was also no significant difference in the rate of in-hospital mortality, occurring in 9% of those without a prior stroke, compared with 13% of those with a recent prior stroke. But the patients with no stroke history fared better by other measures, with a significantly lower rate of in-hospital death or discharge to a hospice, and also a significantly higher rate of 0-1 scores on the modified Rankin Scale, compared with patients with a history of prior stroke.
A more granular analysis of the timing of the prior stroke showed that most of risk from thrombolysis clustered in patients with a very recent prior stroke. The 43 patients with a prior stroke within the preceding 14 days had a symptomatic ICH rate of 16% after thrombolysis, 3.7-fold higher than the control patients in an adjusted analysis. Once the patients with a prior stroke within the past 14 days were pulled out, the remaining patients with prior strokes 15-30 days before as well as those with a prior stroke 31-90 days previously had symptomatic ICH rates that were not significantly different from the controls, Dr. Shah reported.
The results also showed an increased rate of in-hospital mortality or discharge to a hospice clustered in patients treated either within 14 days or during 15-30 days after a prior stroke. In both subgroups, the rate of this outcome was about triple the control rate. In the subgroup treated with thrombolysis 31-90 days after a prior stroke, the rate of in-hospital mortality or discharge to a hospice was about the same as the controls.
“It appears that some patients could benefit from tPA; there is a potential safety signal. It allows for some discretion when using thrombolytic treatment” in patients with a recent, prior stroke, Dr. Shah suggested. “This is by far the largest analysis ever reported” for thrombolytic treatment of patients following a recent, prior stroke, noted, a Duke neurologist and study coauthor.
But, another coauthor, cautioned against immediately applying this finding to practice. “The findings of Dr. Shah’s study suggest that selected patients with prior stroke within a 14- to 90-day window may be considered for tPA treatment. However, further study is warranted given the relatively small number of patients,” said Dr. Fonarow, professor of medicine and cochief of cardiology at the University of California, Los Angeles.
Dr. Shah and Dr. Xian had no disclosures. Dr. Fonarow had no relevant disclosures.
SOURCE: Shah S et al. Stroke. 2019 Feb;50(Suppl_1): .