SAN DIEGO—In a small pilot study, eight of 19 (42 percent) acute stroke patients treated with tissue plasminogen activator (tPA) developed intracranial hemorrhage (ICH), six of whom died, reported James McCallum Noble, MD, Co-chief Resident of the Columbia University Training Program at Harlem Hospital in New York City, here at the American Neurological Association Annual Meeting.
“The bottom line is that among a small group of African-Americans with acute strokes treated with tPA, we found an unexpected rate of poor outcomes, including intracranial bleeds and deaths,” said Dr. Noble, who led the study. This is the first report documenting a high rate of intracranial hemorrhage or death after tPA in African-Americans during the acute phase of stroke treatment, he told Neurology Today.
The retrospective chart review included 19 patients treated at Harlem Hospital in New York City over a five-year period; seven were men and all were African-American. No African-American patients receiving tPA at the hospital during the study period were excluded from the review.
The patients' ages ranged from 43 to 86 years, with a mean age of 70 years. All the patients had a history of hypertension, and all but two were on antihypertensive medication at the time of their strokes.
RAPID CLINICAL DETERIORATION
Although national guidelines for treatment with tPA were followed, five patients showed rapid clinical deterioration associated with intracranial hemorrhage. Four of these patients died. One patient had a large parenchymal hemorrhage contralateral to the area of infarction.
Also, two other patients had hemorrhages with less rapid clinical deterioration; one died, and the other had bled into the area of ischemia as well as the previously unaffected cerebellum.
An eighth patient with petechial hemorrhages within a large infarct had a fatal transtentorial herniation on the fifth hospital day. Two other patients without intracranial hemorrhage also died, one from transtentorial herniation and another from medical complications.
Dr. Noble noted that younger patients tended to have better outcomes. The mean age of the two patients with intracranial hemorrhage who survived was 60 years, compared with a mean age of 78 years among those who died with ICH. Six of the eight patients who developed ICH had a history of coronary artery disease, he said.
“We anticipate criticism in response to the small number of patients in the study,” Dr. Noble said. “But our purpose was to find pilot information after a suspicion of a high rate of complications observed among patients receiving tPA.” Now that these findings confirmed the team's observations, the investigators hope to find possible causes with further study, he added.
While socioeconomic differences may explain the poor outcomes, “our supposition is that it is some factor or factors that are intrinsic to blacks,” Dr. Noble told Neurology Today. “It might be the hypertension that results in chronic vasculopathy or some other ethnically-related difference in how African-Americans respond to IV-tPA.”
The problem will be figuring out how to tease out such factors while accounting for any differences related to socioeconomic status and access to care, he said. Noting that the large African-American community in the Harlem Hospital area of New York City offers an ideal setting for such work, he said his team is pursuing funding for the research.
EXPERT: RESULTS NOT SURPRISING
Commenting on the study, Richard L. Hughes, MD, Associate Professor of Neurology at the University of Colorado Health Sciences Center in Denver, said he was not that surprised by the high rate of ICH in this “high-risk” population.
“If someone asked me what the symptomatic hemorrhage rate would be for a group of 80-year-old diabetics with large MCA [middle cerebral artery] syndromes given IV-tPA at about 180 minutes, I'd have guessed 40 percent, so [the] data aren't so shocking. This is a high-risk cohort, and outcomes with or without IV-TPA are going to be dismal. Ethnicity and gender have been factors in many studies, but I'm never certain how much is socioeconomic and how much is genetic.
“Many centers, including our hospital, prefer to use IA [intra-arterial] lytics in these higher risk cases,” Dr. Hughes noted. “There are some data that support this approach, just not enough to put together evidence-based guidelines.”
ARTICLE IN BRIEF
✓ A small pilot study reported an unexpected rate of poor outcomes, including intracranial bleeds and deaths, among African-Americans with acute strokes treated with tPA.