Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

Abstract

Background: Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage.

Methods: We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 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 to 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.

Results: Among 1000 participants with a mean (±SD) 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 to 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).

Conclusions: The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).

Figure 1. Mean Hourly Minimum Systolic Blood Pressure during the First 24 Hours after Randomization, According to Treatment Group

The dashed vertical line indicates 2 hours, and I bars 95% confidence intervals.

Figure 2. Distribution of Scores on the Modified Rankin Scale, According to Treatment Group

The data are presented only for participants for whom a score on the modified Rankin scale score was obtained at 90 days. The percentage of participants with each score on the modified Rankin scale is shown in or above each cell. Scores range from 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability (able to carry out all usual activities, despite some symptoms), 2 slight disability (able to look after own affairs without assistance but unable to carry out all previous activities), 3 moderate disability (requires some help but able to walk unassisted), 4 moderately severe disability (unable to attend to bodily needs without assistance and unable to walk unassisted), 5 severe disability (requires constant nursing care and attention, bedridden, and incontinent), and 6 death. Percentages may not sum to exactly 100.0 owing to rounding.

Figure 3. Unadjusted Relative Risk of Death or Disability at 3 Months, According to Subgroup

The Glasgow Coma Scale is a measure of level of consciousness, with a score of 3 indicating deep unconsciousness and higher scores indicating milder impairment of consciousness; scores range from 3 to 15. The data are presented only for participants for whom a score on the modified Rankin scale score was obtained at 90 days. Data were missing on the following characteristics: on presence or absence of intraventricular hemorrhage for 4 patients in the intensive-treatment group and 7 in the standard-treatment group; on baseline hematoma volume for 4 in the intensive-treatment group and 7 in the standard-treatment group; on location of hematoma for 4 in the intensive-treatment group and 7 in the standard-treatment group; and on presence or absence of type 2 diabetes mellitus for 10 in the intensive-treatment group and 7 in the standard-treatment group. Data on location of hematoma are not shown for 1 patient in the intensive-treatment group whose hematoma was in the cerebellum (no patient in the standard-treatment group had a hematoma in this location). Data for patients with other or unknown race are not shown. The size of the squares is proportional to the precision of the estimates.