January 6, 2020 – The observational study found that amongst acute ischemic stroke patients treated with intravenous tissue plasminogen activator, patients who had experienced a previous stroke within the past two weeks were especially susceptible to symptomatic intracranial hemorrhage.
Recent findings from the DCRI published in Circulation Cardiovascular Quality and Outcomes shed new light on when it might be risky to use intravenous tissue plasminogen activator (IV tPA) as a treatment for acute ischemic stroke in patients with history of a previous ischemic stroke.
IV tPA has been an approved treatment for acute ischemic stroke since a large trial sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) proved its safety in 1995. However, exclusion criteria for the trial eliminated patients who had experienced a stroke within the past 90 days. Because of the lack of safety data for this group, current guidelines recommend against use of IV tPA for these patients.
However, the DCRI’s Shreyansh Shah, MD, the lead author of the paper, explained, these guidelines are not always adhered to in clinical practice. As providers become more comfortable with using IV tPA, some have begun to use the treatment on types of patients not included in the original trial data. A group at the DCRI decided to conduct an observational study to determine the safety of this practice.
The study, funded by a grant from the American Heart Association to the DCRI’s Ying Xian, MD, PhD, examined a population of 31,987 patients that experienced an ischemic stroke and were treated with IV tPA, comparing a group of patients who had experienced a prior stroke within the past 90 days with a control group of patients with no prior history of stroke. The analysis found that the patients with recent history of stroke were more likely to have adverse outcomes of in-hospital mortality or discharge to hospice. This is likely because patients with previous stroke history have a poorer functional baselines, Shah said.
However, symptomatic intracranial hemorrhage, thought to be the primary risk associated with IV tPA when treating patients who had experienced a recent stroke, was not found at higher rates. The study team conducted a secondary analysis in an effort to further stratify the recent stroke population and identify which patients were truly at higher risk when treated with IV tPA. The secondary analysis found elevated rates of adverse outcomes in patients who experienced a prior stroke within the past 30 days. However, higher rates of symptomatic intracranial hemorrhage were only found in patients who experienced a prior stroke within the last two weeks.
“Beyond two weeks after a prior stroke, our analysis found the risk for intracranial hemorrhage to be similar for patients with history of stroke and patients without,” Shah said. “This analysis suggests that while IV tPA may still be harmful to some patients, that subset may be smaller than we originally thought. More individualized treatment decisions will be necessary in caring for patients who have experienced an acute ischemic stroke, with providers and patients weighing the potential risks and benefits together.”
The patients included in this study were drawn from the Get With the Guidelines-Stroke registry, for which the DCRI acts as a coordinating center. To enable additional analysis, the DCRI also helped link the patients to their Medicare records. Shah said the ability to provide this linkage is one of the greatest strengths of the DCRI’s Outcomes Group, as it enables more longitudinal follow-up and communicates information about specific timing of the patients’ previous stroke.
“This study used real-world evidence to provide useful insights about how clinical practice differs from recommendations outlined by the guidelines,” said the DCRI’s Ying Xian, MD, PhD. “With these results, we can better understand when this derivation from the guidelines may be beneficial for the patient, as well as when it may pose a potential risk.”
Other DCRI contributors to the paper include Adrian Hernandez, MD, MHS; Eric Peterson, MD, MPH; and Li Liang, PhD (statistics). Barbara Lytle served as the DCRI project leader for this project.