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Journal club: Intensive Blood Pressure Lowering in Patients with Acute Cerebral

Hemorrhage

Dr Nowfal Risvan Kaleel Rahman

CT2 ACCS, Wrexham Maelor Hospital

18th August 2016

Introduction

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u  Intra-axial haemorrhage that occurs within the brain tissue

u  Causes include hypertension, neoplasm, trauma, vasculitis, coagulopathy and mycotic aneurysms

u  Distinct from extra-axial haemorrhage (Epidural, subdural and Subarachnoid haematoma)

u  Management typically supportive, BP control, control raised ICP etc

u  Surgical management

Radiology

Source: http://www.radiologymasterclass.co.uk/tutorials/ct/ct_acute_brain/ct_brain_cerebral_haemorrhage

NICE Guidelines- CG68 NICE Guidance -CG68 The study

Published June 8th 2016. DOI: 10.1056/NEJMoa1603460

Overview of study

Population included 1.  Age ≥ 18 year old, GCS >4, haematoma less than 60cm3, within 4.5 hours of symptom onset

2.  One reading of BP ≥ 180mmHg between onset and Tx.

Design Central randomisation, multi-centre, open-label

Intervention Group Target systolic BP 110 to 139 mmHg throughout the 24 hours after randomisation

Standard treatment Group Target systolic BP 140 to 179 mmHg

Primary Hypothesis Intensive treatment will have reduced death or disability at 3 months

Outcome measures Primary: Modified Rankin Scores Secondary: EQ-5D, VAS scores, expansion of haematoma, adverse events

Exclusion

u  Unreliable onset time

u  AVM, neoplasm or aneurysm

u  Related to trauma

u  Pregnancy

u  Bleeding diathesis or coagulopathy or thrombopenia

u  Candidate for immediate surgical intervention

u  ICH affecting Pons or cerebellum

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The ATACH-2 trial

u  Randomised, multi-centre, open-label trial conducted at 110 sites

u  USA, Japan, China, South Korea and Germany

u  500 (intensive treatment) vs 500 (standard treatment) in analysis after screening over 8500

u  Antihypertensive medications titrated to achieve target BP in both groups

u  IV Nircadipine infusion (first line) from 5mg/hr to 15 mg/hr titrated to target. IV labetalol (2nd line)

u  Proportion with Modified Rankin score of 4-6 (severe disability or death): 38.7% in intervention, 37.7% in control

u  Adjusted analysis: Relative risk 1.04 (CI 0.85 – 1.27, p=0.72)

u  Discontinued for futility before target enrolment (1280)

Outcomes Treatment failures

u  Important to see if BP targets were met- main variable in study

u  Statistically significant difference the groups in treatment failure 2 hours after randomisation

u  61 (12.2%) in intervention group vs 4 (0.8%) in control (p<0.001)

u  Same big difference between groups in the 2-24 hour period

u  78 (15.6%) in intervention group vs 7 (1.4%) in control (p<0.001)

Study conclusion

“In conclusion, our results do not support the notion that acute reduction to a target systolic blood pressure of 110 to 139 mm Hg in patients with intracerebral hemorrhage is more effective in improving functional outcome than a reduction to a target systolic blood pressure of 140 to 179 mm Hg”

Strengths of the study

u  Relevant clinical outcomes used e.g. disability and functionality based scores

u  Follow up telephone 1/12 and clinic visit at 3/12

u  Multi-centre across different developed countries

u  Mentions the INTERACT2 trial done previously which didn’t find statistically significant different but many weak points

u  Admitted that trail was powered to identify a difference in risk of 10% or more as they thought it wouldn’t be broadly accepted if any less

Limitations of study

u  Underpowered for many parameters (P values)

u  Would benefit from a larger sample size – their calculation was based on an effect size difference of at least 10%

u  What happened to the 8532 people screened initially (not in main article)

u  Significant difference between treatment failures in the two groups

u  Are the results conclusive based on the treatment failure difference?

Questions?