Blood Pressure Management in ICH: ATACH-2 Trial with a Focus on the Meds

Does intensive blood pressure control improve outcomes and reduce hematoma expansion in acute intracerebral hemorrhage (ICH)? The INTERACT-2 trial previously compared intensive vs. conservative blood pressure control in ICH patients and found no difference in death or disability between the two groups. Enter the ATACH-2 trial, published in the New England Journal of Medicine September 15, 2016. Dr. Ryan Radecki provides his review of the article on his EM Lit of Note site.

The purpose of this post is to evaluate the antihypertensive regimens used. Were they appropriate and are they applicable to practice everywhere?

ATACH-2 Trial Summary

Briefly, patients with ICH (and GCS ≥ 5) were randomly assigned to a systolic blood pressure (BP) target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment). IV antihypertensive medications had to be administered within 4.5 hours of symptom onset. The primary outcome was the proportion of patients who had moderately severe or severe disability or who had died (modified Rankin scale score, 4 to 6) at 3 months. Secondary outcomes were the scores on the EQ-5D utility index and visual-analogue scale at 3 months and the proportion of participants with expansion of 33% or more in the volume of the hematoma on the CT scan obtained at 24 hours after randomization, as compared with the entry scan. Five hundred patients were randomized to each group and the study was ended early as a result of futility. There was no statistically significant difference between the groups in any of the primary or secondary outcomes in either the unadjusted or adjusted analyses.

Antihypertensive Medication Therapy Approach

  • Before randomization, IV antihypertensive medication, including nicardipine, could be administered to lower the systolic blood pressure to less than 180 mm Hg (patients were not eligible if the systolic blood pressure was lowered to less than 140 mm Hg).
  • After randomization, an IV nicardipine infusion starting at 5 mg/hr was the first-line option
    • The rate could be increased by 2.5 mg/hr every 15 minutes up to a maximum dose of 15 mg/hr
    • If the systolic BP was higher than the target, despite infusion of the maximum dose of nicardipine for 30 minutes, IV labetalol was used.


    • Primary treatment failure was defined as not reaching the target BP within 2 hours after randomization.
    • Secondary treatment failure was defined as the hourly minimum systolic BP remaining higher than the upper limit of the target range for 2 consecutive hours during the period of 2 to 24 hours after randomization.
    • This was an open-label trial with no blinding of treatment assignment.

What They Reported

  • Mean minimum systolic BP 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.
  • The mean time to nicardipine initiation in the intensive-treatment arm was 149 minutes vs. 165 minutes in the standard-treatment arm.
  • It isn’t clearly described, but according to Figure 1, the intensive-treatment group reached goal BP in about 30 minutes, while the standard-treatment group reached goal BP in about 15 minutes.
  • Titration of nicardipine and use of labetalol (or other) was not reported.

Application to Clinical Practice

  • Despite clear definitions for BP goals, medication administration parameters, and treatment failures, there is minimal data reported regarding medications (including the Supplementary Appendix).
  • There was not an increased risk of hypotension in the intensive-treatment group.
  • The trial utilized standard, widely available, IV antihypertensive medications with (apparent) proper dose titration of nicardipine (though adherence to the protocol was not reported).

Take-Home Point

The ATACH-2 trial protocol used appropriate IV antihypertensive therapy and the results demonstrate no difference in patient-oriented outcomes between intensive or standard-treatment of BP after ICH.

Author: Bryan D. Hayes, PharmD

Attending Pharmacist, Emergency Medicine and Toxicology, Massachusetts General Hospital; Assistant Professor of EM, Harvard Medical School

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