Effects of tPA Depend on Patient's Gender, Researchers Find

Thomas S. May, MA

Men with acute ischemic stroke are more likely to benefit from intravenous recombinant

tissue plasminogen activator (rtPA) than women with the same condition, according to a

study published in the March 13, 2007, issue of Neurology.

In a secondary analysis of the Glycine Antagonist in Neuroprotection (GAIN) Americas trial (Ref), a team of researchers led by Mitchell Elkind, MD, MS, Associate Professor of Neurology at Columbia University Medical Center, found that male stroke patients receiving rtPA were more than 3 times as likely to be functionally independent at 3 months than female patients who were treated with rtPA.

"There is a lot of evidence suggesting that women have worse outcomes after stroke than men," Dr. Elkind told CNS News.  "We looked at a group of patients who were treated with tPA in a large clinical trial, and we found that women still had a worse outcome than men, in terms of their functional state, three months after their stroke," Dr. Elkind said. "This difference was present even after adjusting for the age of the patients, the severity of the stroke, and other potential confounders." 

 The GAIN Americas trial investigated the efficacy of gavestinel, a putative neuroprotective agent, in over 1,300 patients with ischemic stroke. 333 (24%) of these patients received IV rtPA within 3 hours of onset. Elkind's team found that men treated with rtPA were significantly more likely to achieve good functional outcome at 3 month, compared to women treated with rtPA. 47.5% of men vs 30.3% of women had a Barthel Index (BI) ≥ 95, and 32.2% of men vs 23.4% of women had a modified Rankin Score (mRS) ≤ 1.

After adjusting for age, stroke severity, hypertension, diabetes, and other relevant covariates, men were more than three times as likely to achieve BI ≥ 95 (adjusted OR 3.28, 95% CI 1.74 to 6.17) and more than twice as likely to achieve mRS ≤ 1 (adjusted OR 2.12, 95% CI 1.11 to 4.03) at 3 month, despite the fact that survival was lower among men (adjusted OR 0.45, 95% CI 0.20 to 1.01).

Although previous studies have shown that women tend to do worse after stroke, this is one of the first studies to look specifically at a group of patients who were treated with tPA in the context of a clinical trial, according to Dr. Elkind. "One may have been wondering whether there might have been differences in the approach to the treatment of women, compared with men," he said. "But in this study, women and men were treated equally aggressively, and yet these differences in outcomes still exist."

These results contradict the findings of a previously published meta-analysis (Stroke 2005;36:62-65) that found no difference or a relatively greater benefit in women, pointed out Larry Goldstein, MD, Professor of Medicine and Director of the Duke Center for Cerebrovascular Disease. It is not clear why the results of the study by Elkind and colleagues differ from those of previous studies, according to Dr. Goldstein. He noted, however, that the present study was a non-randomized, post-hoc, exploratory analysis. "Potential confounders were controlled," he said, "but this is not the same as a prospective randomized trial, and there may be unmeasured biases that could affect the results."

Because the analysis was exploratory, no definitive conclusions can be reached, according to Dr. Goldstein. "Additional work needs to be done to help understand why stroke outcomes might differ between men and women," he said.

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