BOSTON – Intensive systolic blood pressure reduction did not significantly reduce hematoma expansion, compared with standard systolic blood pressure reduction in the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II trial, but, in a post hoc analysis, it did show a strong trend toward reducing hematoma expansion in those with a larger initial hematoma volume.
In 450 patients randomized to receive intensive treatment and 426 randomized to receive standard treatment in the large, international, phase III randomized trial, the proportion of patients with any hematoma expansion was 46.4% and 52.3% , respectively (relative risk, 0.89; 95% confidence interval, 0.73-1.07). The proportion with hematoma expansion with an increase of greater than 33% was 18.9% and 24.4%, respectively (RR, 0.77; 95% CI, 0.58-1.03),, reported at the annual meeting of the American Academy of Neurology.
The confidence intervals suggested only a trend toward improvement, as the difference between the groups did not reach statistical significance, he said.
To determine if intensive systolic blood pressure reduction might have more of an impact among higher-risk patients, the investigators conducted a post hoc, secondary analysis in those with relatively larger hematomas. Among patients with an initial hematoma volume of at least 10 mL (at least half of the study population had smaller hematomas), the proportion with any hematoma expansion was 53.8% in the intensive treatment group and 61.3% in the standard treatment group (RR, 0.88; 95% CI, 0.67-1.13), and the proportion of patients with hematoma expansion of greater than 33% was 18% and 27.6%, respectively (RR, 0.67; 95% CI, 0.45-1.00), said Dr. Goldstein of Massachusetts General Hospital, Boston.
In those with an expansion greater than 33% and a hematoma volume of at least 6 cc, the finding was similar.
“The trend looks a little bit more aggressive,” he said, but the 95% confidence interval in those with larger hematomas reached 1.
Study subjects had elevated blood pressure at arrival, ascore of at least 5, and a hematoma volume of less than 60 cc. They were enrolled and randomized within 4.5 hours of symptom onset. Those in the intensive treatment group were treated with a goal of achieving between 110 and 139 mm Hg within 24 hours, and those in the standard treatment group were treated with a goal of achieving between 140 mm Hg and 179 mm Hg within 24 hours. They underwent baseline and 24-hour computed tomography scans, which were analyzed centrally by blinded investigators who recorded any increase of 0.5 mL or more, an increase of more than 33% , an increase of more than 33% or more than 6 mL, and an intraventricular hemorrhage volume greater than 2 mL.
These measures were correlated with death and disability, and hematoma enlargement was shown to be significantly associated with those outcomes at 3 months after randomization (RR, 1.59; 95% CI, 1.25-2.02), Dr. Goldstein said.
Previous studies have suggested that intensive lowering of systolic BP in patients with intracerebral hemorrhage can reduce the rate of hematoma expansion. As such, the hypothesis of the current study was that the intensive treatment of elevated blood pressures – arriving systolic blood pressure of greater than 180 mm Hg – would reduce the likelihood of death and disability at 3 months, Dr. Goldstein said,
The question is whether the biomarker – hematoma expansion – is really linked to clinical outcome, he said, “because a lot of our attempts to treat hematoma expansion are based on the assumption that, if we reduce hematoma expansion, we’re going to improve clinical outcomes.”
“In this trial ... the expanders had more death and disability than nonexpanders, and this was statistically significant, so hematoma expansion does seem to be a statistically significant predictor of poor outcome,” he said.
Thus, the strong trend toward a reduced risk of hematoma expansion with intensive blood pressure lowering in patients with larger hematoma volumes at baseline in this analysis is noteworthy, he said.
“It appears that the treatment is affecting the biomarker, that the treatment is affecting hematoma expansion ... and hematoma expansion was a significant predictor of death and disability ... so why didn’t we get the result we wanted from the trial?” he asked.
It may be that a greater magnitude of reduction in the risk of hematoma expansion was necessary, he said.
“In other words, even if our treatment is having an effect, it’s just not having a big enough effect to change outcomes,” he said, adding that future trials probably need to involve a much bigger impact on the risk of expansion to translate to a change in clinical outcomes.”
This study was sponsored by the National Institute of Neurological Disorders and Stroke. Dr. Goldstein reported having no disclosures.