ATACH-2 Trial


Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

Qureshi et al. NEJM 2016 DOI: 10.1056/NEJMoa1603460

Clinical Question

  • In patients with acute intracerebral haemorrhage and who are hypertensive, does rapid lowering of systolic blood pressure compared to standard therapy improve patient outcomes ?


  • Randomised, multi-centre, open-label
  • Central randomisation using trial website by minimisation algorithm combined with biased-coin method
  • Follow up period of 3 months
  • Power calculation based on assumption that death or disability would be 10% lower in intervention group. Expected control event rate of 60%.
    • alpha error 0.05, power 90%
    • Sample size of 1280 required taking into account non-adherence
  • Intention-to-treat analysis


  • 110 sites in United States, Japan, China, Taiwan, South Korea and Germany
  • May 2011 to September 2015


  • Inclusion:
    • 18 years and above
    • GCS > 4
    • Intraparenchymal haematoma of less than 60cm3 on initial CT scan
    • Within 3 hours (extended to 4.5 hours) of symptom onset
    • At least one reading of systolic blood pressure of 180 mmHg or more between symptom onset and the initiation of intravenous antihypertensive treatment

  • Exclusion:
    • Time of symptom onset not reliably established
    • Previously known AVM, neoplasm or aneurysm
    • Intracerebral hematoma considered to be related to trauma.
    • lCH located in infratentorial regions such as pons or cerebellum
    • IVH associated with intraparenchymal hemorrhage and blood completely fills one lateral ventricle or more than half of both ventricles
    • Subject is considered a candidate for immediate surgical intervention by the neurosurgery service
    • Pregnancy or parturition within previous 30 days or active lactation
    • Any history of bleeding diathesis or coagulopathy
    • Use of warfarin within the last 5 days
    • A platelet count less than 50,000/mm3
    • Known sensitivity to nicardipine
    • Pre-morbid mRS of 4 or greater
    • Subject’s living will precludes aggressive ICU management
  • 8532 patients screened, 1000 randomised


  • * Treatment could be initiated before randomisation to lower the systolic blood pressure to less than 180 mmHg but were excluded if systolic BP reduced below 140 mmHg before randomisation
  • Target systolic BP 110 to 139 mmHg throughout the 24 hours after randomisation


  • Target systolic BP 140 to 179 mmHg throughout the 24 hours after randomisation

Management common to both groups

  • 1st line = IV nicardipine infusion
    • initiated at 5mg/hr, increased by 2.5mg/hour every 15 minutes as needed, up to a maximum dose of 15mg/hr
  • 2nd line (if target not achieved after 30 mins) = IV labetalol (IV diltiazem or urapidil if labetolol not available)


  • Primary outcome:
    • Proportion of patients who had modified Rankin scores 4 to 6 at 3 months (significant disability or death)
      • No difference between groups (38.7% in intervention, 37.7% in control)
        • Unadjusted analysis: relative risk 1.02 (CI 0.83 – 1.25, p=0.84)
        • Adjusted analysis: relative risk 1.04 (CI 0.85 – 1.27, p=0.72)
  • Secondary outcome:
    • Unadjusted analysis showed no difference between groups in:
      • EQ-5D scores at 3 months
      • VAS at 3 months
      • Proportion of patients with expansion of 33% or more in volume of haematoma on 24 hour scan compared to baseline scan
      • Safety outcomes (fall in GCS by 2 or increase of NIH Stroke Score by 4)
      • Incidence of serious adverse events within 72 hours
    • Higher incidence of serious adverse events within 3 months in intervention group when analysis adjusted
      • 25.6% in intervention, 20% in control; p=0.05


  • Primary treatment failure = not achieving target within 2 hours after randomisation
    • 61 (12.2%) in intervention arm, 4 (0.8%) in control arm; p<0.001
  • Secondary treatment failure = hourly minimum systolic BP above target range for 2 consecutive hours during the period of 2 to 24 hours after randomisation
    • 78 (15.6%) in intervention arm, 7 (1.4%) in control arm; p<0.001

ATACH2 tableAuthors’ Conclusions

  • The results of the trial do not support the reduction of systolic blood pressure to a target of 110 to 139 mmHg in patients with intracerebral haemorrhage


  • Multi-centre trial
  • Clinically meaningful and relevant outcome measures


  • Recruitment criteria changed during the trial
  • Reasons for failure to randomise screened population not included
  • Under-powered – power calculations based on event rate of 60%, actual observed event rate in study of 38%, increasing likelihood ot type 2 error
  • More than 50% of patients recruited from Asia sites and may not be reflective of European population
  • Intracerebral haemorrhage grouped as a single entity
  • Significant difference between groups with regards to treatment failure (primary and secondary)

The Bottom Line

  • The results of this trial and that of the INTERACT2 trial do not support an early, intensive control of systolic blood pressure in patients with acute intracranial haemorrhage

External Links


Summary author: Adrian Wong
Summary date: 15 July 2016
Peer-review editor: Duncan Chambler


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