While the American Heart/Stroke Association still categorizes a history of intracranial hemorrhage (ICrH) as a contraindication to the use of intravenous thrombolysis (IVT), this alert was removed from alteplase's prescribing information due to lack of evidence. Further, the use of IVTs in patients with prior ICrH is not mentioned in the 2021 European Stroke Organization guidelines. This renders the use of IVTs in acute ischemic stroke (AIS) patients with prior ICrH somewhat controversial.

To help clarify the safety of the use of IVTs for AIS in patients with a history of ICrH, investigators performed a meta-analysis comparing the use of these drugs in patients with AIS who had and who did not have a history of ICrH. In this study, prior ICrH referred to any history of intracranial hemorrhage, subarachnoid hemorrhage, subdural hematoma, or epidural hematoma. ICrH was defined by clinical history, imaging, or both. Symptomatic hemorrhagic transformation (sHT) was defined as an in-hospital clinical deterioration of >4 points in the National Institutes of Health Stroke Scale.

PubMed, Embase, and Cochrane databases were searched through April 2020. Outcome measures included the rate of sHT; 90-day Modified Rankin Scale (mRS; mRS is used to measure the degree of disability in patients who have had a stroke); and death within 90 days. A 90-day mRS score of 0-1 was considered a favorable clinical outcome.

Studies that enrolled patients with AIS or imaging findings in favor of prior ICrH with or without a history of ICrH prior to the index AIS; that enrolled patients who received IVT despite a previous history of ICrH; and that provided data on the outcome measures specified were eligible for inclusion.

A total of seven retrospective observational studies were included in this meta-analysis. There was no significant difference in the rate of sHT between patients with or without a history of ICrH following IVT. This finding was confirmed in studies that included both a positive medical history and imaging findings of ICrH, as well in those clinical trials that employed standard-dose IVT.

However, there was a significant difference in the frequency of death following IVT in patients with and without a history of ICrH. Based on the results of two trials, death within 90 days of IVT was 17.6% in those with a history of ICrH versus 5.5% in those without a prior history of ICrH (odds ratio [OR] = 3.91, 95% CI, 2.16-7.08, P <.00001).

Among the four studies (n = 3073) that reported on 90-day mRS scores, there were significantly lower rates of favorable outcomes (mRS score of 0-1) in patients with prior ICrH (OR = 0.54, 95% CI, 0.35-0.84, P = .006) compared with 38.1% of patients without a previous history of ICrH.

Conversely, there were higher rates of unfavorable outcomes (defined as a mRS of 4-6) in patients with prior ICrH compared with those without prior ICrH (OR = 1.57, 95% CI, 1.07-2.30, P = .02). Use of standard-dose IVT did not affect these results.

For hospital pharmacists managing critically ill patients, this study provides both reassurance and concern that while the use of IVT in AIS patients with a prior history of ICrH does not increase the risk of sHT, it is associated with higher 90-day mortality rates and less favorable 90-day functional outcomes.

Such information offers valuable insight for team-based decisions in the management of patients with AIS. However, it is also important to note that this study was based on nonrandomized trials and may be subject to a high risk of selection bias.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

« Click here to return to Infusion Pharmacy Update.