NEW YORK -- Men given thrombolysis for acute ischemic stroke were three times more likely than women to have a good functional outcome, despite elevated mortality, researchers here reported.
NEW YORK, March 13 -- Men given thrombolysis for acute ischemic stroke were three times more likely than women to have a good functional outcome, despite elevated mortality, researchers here found.
The findings came from a secondary analysis of the multicenter randomized study known as the Glycine Antagonist in Neuroprotection (GAIN) Americas trial, reported Mitchell Elkind, M.D., of Columbia University, and colleagues, in the March 13 issue of Neurology.
In that the GAIN study, published in 2001 in the Journal of the American Medical Association, 1367 ischemic stroke patients were randomized to placebo or gavestinel, an antagonist of the glycine site of the N-methyl-D-aspartate receptor. Gavestinel administered up to six hours after an acute ischemic stroke did not improve functional outcome at three months.
Of these patients, 333 (24%) were also treated within three hours of stroke onset with a recombinant tissue plasminogen activator. The current study is a secondary analysis of the tPA-treated patients. Women (150, mean age 69.5) were slightly older than the men (183, mean age 66.3).
Functional independence at three months, the primary outcome, was defined by the Barthel Index (BI). Favorable outcomes were BI ? 95 (versus < 90 or dead).
Secondary outcomes were the modified Rankin Score (mRS) and NIH Stroke Scale (NIHSS) for stroke severity, and mortality. Good outcomes for this analysis were modified Rankin Score of ? 1, and NIHSS ? 1, and three-month survival.
After adjusting for a list of relevant covariates, men were more likely to have good outcomes for functional independence (BI), with an adjusted odds ratio (OR) 3.28 (95% CI, 1.74 to 6.17), the researchers reported. For modified Rankin Score ? 1, the adjusted OR for men was 2.12 (CI, 1.11 to 4.03).
However, survival was worse among men: adjusted OR 0.45 (CI, 0.20 to 1.01), the researchers reported.
Looking at functional independence at three months, 47.5% of men versus 30.3% of women had a BI ? 95, while 32.2% of men versus 23.4% of women had modified Rankin Score ? 1. The NIH Stroke Scale was similar by gender.
There are biologic reasons why women may have a less favorable response to thrombolysis than men, Dr. Elkind and colleagues wrote. Elevated circulating levels of procoagulant factors in women with coronary artery disease may be a factor.
In addition to gender, the researchers said that the analysis found other prognostic indicators of functional outcomes among tPA-treated patients, including age, stroke severity, and stroke-related and infectious complications. Also, left hemispheric stroke patients had more than twice the likelihood of a favorable outcome, a finding consistent with other studies.
These results are similar to those of other studies showing that women have worse functional outcomes after stroke, and the results findings extend to women treated with tPA, the researchers said.
Studies have found that women have higher levels of procoagulant factors, such as plasminogen activator inhibitor and factor VII than men. It is possible, they said, that these procoagulant factors might result in more resistance to thrombolysis and therefore worse outcomes.
Study limitations included the lack of data on several factors important to stroke outcome, such as admission glucose levels, temperature, or timing of thrombolysis. The small number of outcomes also limited the ability to consider other potential confounders, such as concomitant medication.
Although there were imbalances in stroke severity between men and women, these differences were not significant, and adjustment was made in multivariable analyses. Also, data on rtPA dosing, timing, and the rate of recanalization were not available, the researchers said.
Information from this study may prove useful to those planning clinical trials of putative neuroprotective agents in which patients will be enrolled after receiving thrombolysis. Investigators may need to consider stratification by sex in enrollment and might also consider adjusting future analyses by sex, the researchers concluded.