Blood Pressure Lowering in Acute Cerebral Hemorrhage
What is the efficacy of rapidly lowering the systolic blood pressure level in patients in an earlier time window after symptom onset when treating acute hypertensive response in patients with intracerebral hemorrhage?
The ATACH-2 trial investigators randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm3) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3-15, with lower scores indicating worse condition) to a systolic blood pressure target of 110-139 mm Hg (intensive treatment) or a target of 140-179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4-6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments.
Among 1,000 participants with a mean (± standard deviation) systolic blood pressure of 200.6 ± 27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85-1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, p = 0.002).
The authors concluded that treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110-139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140-179 mm Hg.
This study reports that intensive reduction in the systolic blood pressure level of participants with intracerebral hemorrhage does not provide an incremental clinical benefit. It is possible that the blunting of fluctuations in the systolic blood pressure level in patients with intracerebral hemorrhage and an acute hypertensive response may exert a therapeutic benefit that is independent of the magnitude of lowering the systolic blood pressure level. There was a higher occurrence of serious adverse events within 3 months after randomization among participants who were randomly assigned to intensive treatment than among those randomly assigned to standard treatment. Based on this and other available evidence, intensive blood pressure lowering in patients with acute cerebral hemorrhage does not appear to be the recommended strategy.
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