No Clinical Benefit With Intensive Blood-Pressure Lowering in Acute Cerebral Hemorrhage Interview with:
Adnan I. Qureshi, M.D
Zeenat Qureshi Stroke Research Center
University of Minnesota
Minneapolis, MN What is the background for this study? What are the main findings?

Dr. Qureshi: An acute hypertensive response in patients with intracerebral hemorrhage is common and may be associated with hematoma expansion and increased mortality. The Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial was designed to determine the efficacy of rapidly lowering systolic blood pressure in patients in an earlier time window after symptom onset than evaluated in previous trials. The trial was based on evidence that hematoma expansion and subsequent death or disability might be reduced with very early and more aggressive reduction in systolic blood pressure in those at higher risk due to presence of high systolic blood pressure at presentation. The trial randomized eligible subjects with intracerebral hemorrhage to test the superiority of intensive (goal 110-140 mmHg) over standard (goal 140-180 mmHg) systolic blood pressure reduction using intravenous nicardipine within 4.5 hours of symptom onset. Of a total of 1000 subjects that were recruited with a mean (standard deviation) baseline systolic blood pressure of 200.6 (27.0) mmHg, 500 were assigned to intensive-treatment and 500 to standard-treatment. Enrollment was stopped following a pre-specified interim analysis because of futility.

The primary endpoint of death or disability at 3 months post-randomization was observed in 38.7% (186/481) of subjects receiving intensive treatment and 37.7% (181/480) subjects receiving standard treatment (relative risk: 1.03; 95% confidence interval: 0.85 to 1.27), adjusted for age, initial Glasgow Coma scale, and presence or absence of intraventricular hemorrhage. The rate of renal adverse events within 7 days of randomization was significantly higher among subjects randomized to intensive treatment. Compared to a target systolic blood pressure of 140-180 mmHg, treating subjects with intracerebral hemorrhage to a target systolic blood pressure of 110-140 mmHg did not lower the rate of death or disability. What should readers take away from your report?

Dr. Qureshi: The ATACH-2 results suggest that intensive systolic blood pressure reduction does not show incremental clinical benefit. The absolute difference in rates of death or disability between the two groups was 1%. The study was powered to identify a 10% or greater absolute risk reduction with intensive treatment as smaller risk reduction was expected to be viewed as insufficient for broad acceptance of a new intervention. We had postulated that more rapid intensive SBP reduction and exclusion of patients with no requirement for IV antihypertensive medication would make it more likely to demonstrate a larger magnitude of therapeutic benefit, but our results did not confirm this hypothesis.
It should be noted that ATACH-2 is not representative of patients with large intracerebral hemorrhages, intracranial pressure elevation, and compromised cerebral perfusion pressure. Therefore, the possibility of precipitating global or regional cerebral hypoperfusion with intensive systolic blood pressure reduction in such patients may still be a concern. Although lowering systolic blood pressure to <140 mmHg is probably safe, our results do not support the notion that acute systolic blood pressure reduction to a target systolic blood pressure 110-140 mmHg in patients with intracerebral hemorrhage is effective in improving functional outcome compared with reduction to a target systolic blood pressure of 140-180 mmHg. What recommendations do you have for future research as a result of this study?

Dr. Qureshi:  The observed rate (37.7%) of death or disability at 3 months was lower than the rates (60%) anticipated in trial design based on previous literature. A reason for high proportion of favorable outcomes may be monitoring and standardizing intensity of medical care provided at each site and low rates of withdrawal of care among subjects recruited in the study (compared with a 34% rate outside clinical trials). Such observations suggest that standardization of intensity of medical care can result in lower than expected rates of death and disability in patients with intracerebral hemorrhage. Thank you for your contribution to the community.


Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage
Adnan I. Qureshi, M.D., Yuko Y. Palesch, Ph.D., William G. Barsan, M.D., Daniel F. Hanley, M.D., Chung Y. Hsu, M.D., Renee L. Martin, Ph.D., Claudia S. Moy, Ph.D., Robert Silbergleit, M.D., Thorsten Steiner, M.D., Jose I. Suarez, M.D., Kazunori Toyoda, M.D., Ph.D., Yongjun Wang, M.D., Haruko Yamamoto, M.D., Ph.D., and Byung-Woo Yoon, M.D., Ph.D., for the ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network*
June 8, 2016DOI: 10.1056/NEJMoa1603460

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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