Hans Christophe Diener discusses the treatment of patients with intracerebral hemorrhage.
The ATACH-II (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial — showing that very intensive blood pressure reduction is no better than standard blood pressure lowering in the emergency treatment of patients with acute hemorrhagic stroke — has now been published online in the New England Journal of Medicine (NEJM).
The study was first presented, and reported by Medscape Medical News (including discussion from outside experts), last month at the European Stroke Organisation Conference (ESOC) 2016 in Barcelona, Spain.
In the NEJM paper, the authors, led by Adnan I. Qureshi, MD, University of Minnesota, Minneapolis, conclude: “Our results do not support the notion that acute reduction to a target systolic blood pressure of 110 to 139 mm Hg in patients with intracerebral hemorrhage is more effective in improving functional outcome than a reduction to a target systolic blood pressure of 140 to 179 mm Hg.”
The trial follows on from the INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2), reported in 2013, which did suggest a benefit of lowering blood pressure in these patients. But the ATACH-II investigators point out some key differences between the two trials that may explain the seemingly different results.
They note that in ATACH-II, the mean minimum systolic blood pressure in the first 2 hours after randomization was 128.9 mm Hg in the intensive-treatment group and 141.1 mm Hg in the standard-treatment group. In contrast, INTERACT2 found that the mean systolic blood pressure was 150 mm Hg in the first hour in the intensive-treatment group and 164 mm Hg in the standard-treatment group.
“Thus, the early profile of the systolic blood-pressure level in the standard-treatment group in the ATACH-II trial was similar to values observed early in the intensive-treatment group in INTERACT2. We had postulated that a more rapid intensive reduction in the systolic blood-pressure level than that used in INTERACT2 and the exclusion of patients with no requirement for intravenous antihypertensive medication would make it more likely to show a larger magnitude of therapeutic benefit, but our results did not confirm this hypothesis,” the authors state.
They add: “The results of our trial suggest that intensive reduction in the systolic blood-pressure level does not provide an incremental clinical benefit. It is also 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.”
More Renal Adverse Events
The ATACH-II trial also showed 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.
While serious adverse events related to treatment within 72 hours after randomization were not increased in the intensive group, a post hoc comparison suggested a higher proportion of renal adverse events within 7 days after randomization in the intensive-treatment group.
For the study, patients with intracerebral hemorrhage (volume < 60 cm3) and a Glasgow Coma Scale (GCS) score of 5 or more were randomly assigned 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). Blood pressure was lowered in both groups with intravenous nicardipine administered within 4.5 hours after symptom onset.
Enrollment was stopped because of futility after a prespecified interim analysis when 1000 participants had been included (500 in each group). Mean systolic blood pressure at baseline was 200.6 mm Hg. The mean age of the patients was 61.9 years, and 56.2% of patients were Asian.
The primary outcome of death or disability (modified Rankin scale score of 4 to 6) at 3 months occurred in 38.7% of the intensive-treatment group and 37.7% of the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 – 1.27). The 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 = .002).
The ATACH-II trial was funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center. Dr Qureshi reports grant support from the National Institute of Neurological Disorders and Stroke and nonfinancial support from Chiesi USA and Astellas Pharma during the conduct of the study.
N Engl J Med. Published online June 8, 2016. Abstract
ATACH-II Published: Intensive BP Reduction Not Needed in ICH