Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

Published - Written by Andrea Merrill

What is the ideal blood pressure goal for spontaneous cerebral hemorrhage? Results of the ATACH-2 trial are discussed.

As a surgery resident, one of the first concepts I learned was that high blood pressure was bad in a patient who was actively bleeding.  This meant that for a trauma patient with a large liver or splenic laceration, systolic blood pressure should be kept around 90 mm Hg.  Similarly, for a ruptured abdominal aortic aneurysm, one of our first steps in management is to place the patient on an esmolol drip to get the blood pressure down.  Intuitively, this makes sense — high pressure increases the rate of bleeding, likely leading to worse clinical outcomes and even death.  This concept might also apply to spontaneous cerebral hemorrhage, however, here there is also good reason to be concerned that lowering blood pressure could be harmful. In stroke, rapid blood pressure lowering is thought to adversely affect neurological outcomes.   The INTERACT-2 trial published in NEJM in 2013, did not show a significant difference in rate of death or severe disability with intensive systolic blood pressure lowering (to <140 mm Hg) within 6 hours of symptom onset as compared with standard blood pressure goals of <180 mm Hg.

While INTERACT-2 was a negative trial, there were findings that suggested that earlier intensive blood pressure lowering might have benefits. Recently published Online First in NEJM, Qureshi et al. investigate whether earlier intensive blood pressure lowering may improve outcomes in spontaneous cerebral hemorrhage in the ATACH-2 trial.

This multicenter, randomized, unblinded, open-label trial compared intensive systolic blood pressure lowering (goal systolic blood pressure 110-139 mm Hg) to standard anti-hypertensive treatment  (goal systolic blood pressure 140-179 mm Hg) initiated within 4.5 hours of symptom onset in patients with spontaneous supratentorial intracerebral hemorrhage and at least one systolic blood pressure reading of 180 mm Hg or more.  Patients were required to have a Glasgow Coma Scale (GSC) of 5 or more and a hematoma of less than 60cm3.  Assigned blood pressure control was continued for 24 hours.  Intravenous nicardipine was the first line anti-hypertensive followed by intravenous labetolol (or diltiazem or urapidil if labetolol unavailable).  The primary outcome was the proportion of patients who had moderately severe or severe disability (based on the Rankin score) or death at 3 months.  Secondary outcomes included quality of life (measured by the EQ-5D questionnaire or the proportion of patients with 33% expansion of the hematoma on repeat CT scan after 24 hours.

In this analysis with 500 patients in each arm, the mean systolic blood pressure in the intensive-treatment group was about 130 mm Hg versus about 140 mm Hg in the standard-treatment group.  Failure to achieve target blood pressure control within 2 hours occurred in about 12% in the intensive- treatment group compared to less than 1% in the standard-treatment group.

The rate of the primary outcome of death or disability was similar between the two groups, both close to 38%.    There was also no difference in quality of life, percentage of patients with hematoma expansion, rates of death at 3 months or in neurologic deterioration at 24 hours after randomization.  While there was no difference in immediate adverse events, there was a higher risk of adverse events in the intensive-treatment group in the 3 months after randomization compared to the standard group (~25% vs 20% p=0.05).  Specifically, there were more renal adverse events in the intensive-treatment group (9% vs 4%, p=0.002).

Overall, the results of the study are similar to those in the INTERACT-2 trial; there was no significant difference in death or disability with intensive blood pressure lowering compared with standard blood control.  These findings do not support intensive blood pressure lowering in spontaneous intracerebral hemorrhage.

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Andrea Merrill, MD

Andrea was a 2015-2016 NEJM Group Editorial Fellow. She is currently in the middle of her General Surgery residency at Massachusetts General Hospital and is also conducting research focusing on improvements in breast cancer surgery. She plans to pursue a fellowship in Surgical Oncology at the completion of her residency.