Shreyansh Shah, MDShreyansh Shah, MBBS
Patients who have had a prior ischemic stroke in the previous 14 days face an increased risk for intravenous tissue plasminogen activator- (IV tPA) related intracranial hemorrhage, according to results of a retrospective observational study published in Circulation: Cardiovascular Quality and Outcomes.1

History of recent ischemic stroke is typically considered to be a contraindication for IV tPA, though available studies have had inconsistent results. While the FDA updated the drug label in 2015 to no longer list recent stroke as a contraindication,2 the topic remains hotly debated among physicians.

In order to better understand the risk associated with giving IV tPA to patients with prior ischemic stroke, researchers led by Shreyansh Shah, MBBS, assistant professor of neurology at Duke University School of Medicine, and colleagues evaluated data on treatment complications and in-hospital outcomes of IV tPA from the American Heart Association and American Stroke Association Get With The Guidelines–Stroke registry. They examined the relationship between prior stroke and IV tPA-related outcomes in patients with a history of stroke over the following time periods: 1 to 14, 15 to 30, 31 to 90, 91 to 180, and 181 to 365 days.

Patients included in the analysis were treated with IV tPA within 4.5 hours of symptom onset. Ultimately, data from 31,987 patients (median age, 90) were included. Of those, 293 had a prior stroke within 90 days, 434 between 91 and 180 days, 605 between 181 and 365 days, and 30,655 had no history of stroke. Notably, patients who had a prior stroke within 90 days were more likely than those with no history of stroke to have coexisting medical conditions, including coronary artery disease, diabetes, carotid stenosis, and dyslipidemia. They were also more likely to be on medications, include antiplatelets and antihypertensives. These patients also had a higher initial National Institutes of Health Stroke Scale scores.
 
WATCH NOW: Andrew Russman, DO: Neuroprotection Versus Neurorestoration

Patients with prior ischemic stroke within 90 days had higher rates of symptomatic intracranial hemorrhage than those with no prior history of stroke, though these findings were not statistically significant after adjustment (adjusted odds ratio [aOR] 1.50; 95% CI, 0.95–2.37). Similar non-statistically significant differences were observed for life-threatening or systemic hemorrhage, serious tPA-related complications, and in-hospital mortality rates.

When stratified by time since prior stroke, the only group of patients who had an increased risk for symptomatic intracranial hemorrhage were those who had a stroke within the 14 days prior (16.3% vs 4.8%; aOR 3.7; 95% CI, 1.62–8.43). Notably, the rate of in-hospital mortality/discharge to hospice was 25.9% in patients with prior stroke versus those with no prior history of stroke (17%; aOR 1.70; 95% CI, 1.21–2.38). They were also less likely to be discharged to home (28.3% vs32.3%; aOR 0.72; 95% CI, 0.54–0.98) and to have good functional outcomes at discharge (modified Rankin Scale, 0–1; 11.3% vs 20.0%; aOR 0.46; 95% CI, 0.24–0.89).

“While the current AHA/ASA guidelines recommend that use of IV tPA in patients presenting with AIS who have had a prior ischemic stroke within 3 months may be harmful… findings from our study indicated that the impact of prior stroke on IV tPA outcomes might vary according to the timing of the recent stroke,” the authors wrote. “Physicians need to continue to be vigilant about the safety of IV tPA in patients with more recent prior stroke, and individualized decision-making is needed to judge whether the benefits outweigh the risks for using IV tPA in patients with more remote history of stroke.”
REFERENCES
1. Shah S, Liang L, Kosinski A, et al. Safety and outcomes of intravenous tPA in acute ischemic stroke patients with prior stroke within 3 months: findings from Get With The Guidelines-Stroke. Circ Cardiovasc Qual Outcomes. 2020;13(1):e00603 doi: 10.1161/CIRCOUTCOMES.119.006031.
2. United States Food and Drug Administration label for ACTIVASE. Available at:  accessdata.fda.gov/drugsatfda_docs/label/2015/103172s5203lbl.pdf. Accessed January 8, 2020.