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Aggressive blood pressure lowering in acute intracerebral hemorrhage did not reduce death or disability risk, the ATACH-2 trial showed.
The rate of death or disability at 3 months was 38.7% with a target of 110 to 139 mm Hg systolic in the first 4.5 hours after onset, compared with 37.7% with a standard 140- to 179-mm Hg target (relative risk 1.04, 95% CI 0.85-1.27) after adjustment for age, initial Glasgow Coma Scale score, and presence of intraventricular hemorrhage.
Action Points
- Note that this randomized trial evaluating more versus less-intense blood pressure control after cerebral hemorrhage was terminated early due to futility.
- Be aware that some blood pressure control remains critical for patients with ICH, who typically present with severe hypertension.
Nor was there any ordinal shift in modified Rankin scores, difference in death or disability considered separately, or reduction in the proportion of patients with hematoma expansion, , of the University of Minnesota in Minneapolis, and colleagues reported online in the .
Even in the group expected to benefit most -- those who achieved the target pressure in the first 2 hours -- the difference did not favor intensive treatment (RR 1.02, 95% CI 0.87-1.21).
The findings from this trial, halted early for futility, were not a total surprise, given the failure of a less-than-140 mm Hg target to significantly lessen the primary outcome of death or disability in the INTERACT2 trial, commented , of University Hospitals Case Medical Center in Cleveland, which was an ATACH-2 trial site.
"It suggests that our idea that lowering blood pressure early on would reduce hematoma growth and improve outcomes was overly simplistic," he told MedPage Today in an interview.
, a past president of the American Heart Association and president-elect of the American Academy of Neurology, agreed that ATACH-2 "adds to the evidence that standard blood pressure treatment is just as effective.
"We still need to manage systolic blood pressure, but just not as aggressively as we thought among patients with intracerebral hemorrhage," he concluded, noting that the trial participants arrived with an average systolic blood pressure of 200 mm Hg in the emergency department, well above even the standard-treatment target.
ATACH-2 included 1,000 patients (mean age 61.9, 56.2% Asian) with an intracerebral hemorrhage volume less than 60 cm3 and a Glasgow Coma Scale score of 5 or more. The patients were randomized to systolic blood pressure targeted with IV nicardipine (Cardene) within 4.5 hours after symptom onset.
The trial was stopped early (short of the planned 1,280 participants) at an interim analysis for futility.
But even if the trial had enrolled more participants, it's not clear that there would be more definitive evidence of benefit or harm, commented, of New York-Presbyterian/Columbia University Medical Center.
"Given that neither INTERACT2 or ATACH-2 established benefit or harm, do we need more and larger studies on this important topic? I think the answer is no -- and not because of the main outcome results," he said. "More important to me was the finding that adverse-event rates, and especially acute kidney failure, were significantly higher in the intensive blood pressure goal group."
Treatment-related serious adverse events occurring within 72 hours of randomization were reported in 1.6% of intensive-treatment patients and 1.2% of standard-treatment patients. Renal adverse events within 7 days of randomization occurred in 9.0% versus 4.0% of patients, respectively (P=0.002).
"A larger trial might yield a more definitive statistical result, but it seems unlikely to yield a clinically meaningful result," Moran concluded. "Given that we are more sure that lowering blood pressure in acute hemorrhagic stroke might lead to acute kidney injury and other adverse outcomes, it seems best to 'first do no harm' and for now, follow conservative blood pressure goals in these patients."
However, , of the Centre Hospitalier de l'Universite de Montreal, suggested that the use of only nicardipine might have been responsible for both the lack of benefit in the trial and the renal event imbalance.
"The blood pressure lowering effect in INTERACT 2 (which used many different IV blood pressure lowering drugs) was not associated with any renal side effects," he said in an email to MedPage Today.
strong>From the American Heart Association:
Disclosures
The trial was funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center.
Qureshi reported 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.
Primary Source
New England Journal of Medicine
Qureshi AI, et al "Intensive blood-pressure lowering in patients with acute cerebral hemorrhage" N Engl J Med 2016; DOI: 10.1056/NEJMoa1603460.