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Original Investigation
July 2018

Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial

Author Affiliations
  • 1Division of Neurology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 2Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  • 3J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston
  • 4Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston
  • 5Stroke Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Mondino Foundation, Pavia, Italy
  • 6Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston
  • 7Zeenat Qureshi Stroke Research Center, University of Minnesota, Minneapolis
  • 8Department of Public Health Sciences, Medical University of South Carolina, Charleston
  • 9Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston
JAMA Neurol. 2018;75(7):850-859. doi:10.1001/jamaneurol.2018.0454
Key Points

Question  Do patients with acute intracerebral hemorrhage with vs without cerebral microbleeds have different rates of hematoma expansion, 3-month outcomes, or response to intensive blood pressure lowering?

Findings  In this predefined subgroup analysis of a randomized clinical trial investigating optimal blood pressure lowering in 167 patients with intracerebral hemorrhage, the rates of hematoma expansion and 3-month death or disability did not differ between patients with microbleeds and those without. Patients with microbleeds responded similarly to intensive treatment.

Meaning  Patients with intracerebral hemorrhage with vs without microbleeds have similar rates of hematoma expansion and death or disability at 3 months, without apparent differential response to intensive blood pressure lowering.


Importance  Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease.

Objectives  To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion.

Design, Setting, and Participants  Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses.

Main Outcomes and Measures  The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan.

Results  A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, −1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, −1.08 to 2.31; P = .48).

Conclusions and Relevance  Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment.

Trial Registration  ClinicalTrials.gov Identifier: NCT01176565