By: Dr Tom Moullaali1,2

twitter: @tom_moullaali

European Stroke Organisation (ESO) guidelines on blood pressure (BP) management in acute ischaemic stroke and intracerebral haemorrhage (ICH) were published in May 2021.1 They acknowledge ‘continued uncertainty over the benefits and risks of intensive BP lowering on functional outcome’ and make the following recommendations for patients with acute (<24 hours) ICH: ‘In patients with hyperacute (<6 hours) intracerebral haemorrhage, we suggest lowering BP to below 140 mm Hg (and to keep it above 110 mm Hg) to reduce haematoma expansion.’

The guideline committee reached consensus on two additional recommendations:

  • ‘In patients with acute ICH, we suggest initiating antihypertensive treatment as early as possible and ideally within 2 hours of symptom onset. The decrease of systolic BP should not exceed 90 mm Hg from baseline values.’
  • ‘In patients with acute ICH, we suggest lowering BP according to recommended levels beyond 6 hours after onset of treatment for at least 24 hours and up to 72 hours to reduce haematoma expansion.’

These recommendations were based on meta-analysis of randomised controlled trials that tested effects of various strategies to lower BP within 7 days of acute ICH, where a modest treatment effect on haematoma expansion did not translate to improved functional outcome by 90-180 days.2,3

Therefore, several questions remain. Here are few – please share yours via twitter! @tom_moullaali

Targeting ICH growth to improve outcomes

  • We know most haematoma expansion occurs within the first few hours of ICH onset.4 Are we simply treating patients too late?
  • Only 1 or 2 patients in every 5 patients meet accepted definitions of haematoma expansion measured on serial brain imaging.4 Should we target patients with the highest risk of haematoma expansion? Or accept smaller effects in large patient numbers?

Mechanisms underpinning the potential risks and benefits of BP lowering treatment

  • We know patients with ICH are frequently elderly and comorbid. Are there patient factors that influence the potential risks and benefits of treatment? Recent research shows that comorbid renal impairment may be important.5
  • Most patients in the meta-analyses had relatively small volume, deep ICH. What are the effects of BP lowering in patients with large ICH?

How should we lower BP after acute ICH in clinical practice?

  • There remains uncertainty over the preferred agent for early BP lowering after ICH: Meta-analysis of patient-level data showed that patients with acute ICH who were treated in RCTs where α and β-adrenoreceptors were the most frequently used agent appeared to have better functional outcomes compared with various others.3 RCTs that involved relatively small numbers of patients with acute ICH who received ultra-early transdermal glyceryl trinitrate reported different results.6,7
  • Research has shown associations between higher variability in BP and extreme early reductions in BP and poorer functional outcome after acute ICH.8 Do they have a causal role and if so, how do we avoid these phenomenon in clinical practice?

Ultimately, large patient numbers will be required to provide definitive evidence on these issues. For now, back to the drawing board… I’d love to hear your views @tom_moullaali

Affiliations:
1Centre for Clinical Brain Sciences, University of Edinburgh, UK
2George Institute for Global Health, Sydney, Australia

References

  1. Sandset EC, Anderson CS, Bath PM, et al. European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage. Eur. Stroke J. 2021;6:48–89.
  2. Boulouis G, Morotti A, Goldstein JN, Charidimou A. Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion. Systematic review and meta-analysis of randomised trials. J. Neurol. Neurosurg. Psychiatry 2017;88(4):339–345.
  3. The Blood Pressure in Acute Stroke (BASC) Investigators. Early lowering of blood pressure after acute intracerebral hemorrhage: a systematic review and meta-analysis of individual patient data. J. Neurol. Neurosurg. Psychiatry 2021;in press.
  4. Al-Shahi Salman R, Frantzias J, Lee RJ, et al. Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data. Lancet. Neurol. 2018;17(10):885–894.
  5. Fukuda-Doi M, Yamamoto H, Koga M, et al. Impact of renal impairment on intensive blood-pressure-lowering therapy and outcomes in intracerebral hemorrhage: results from ATACH-2. Neurology 2021;https://doi.org/10.1212/WNL.0000000000012442.
  6. Bath PM, Woodhouse LJ, Krishnan K, et al. Prehospital transdermal glyceryl trinitrate for ultra-acute intracerebral hemorrhage: data from the RIGHT-2 trial. Stroke 2019;50(11):3064–3071.
  7. Uniken Venema S, Van den Berg S, Nederkoorn P, Van Der Worp B. Multicentre randomised trial of acute stroke treatment in the ambulance with a nitroglycerin patch (MR ASAP). Eur. Stroke J. 2021;6(1_suppl):514–543.
  8. Moullaali TJ, Wang X, Martin RH, et al. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage: a preplanned pooled analysis of individual participant data. Lancet Neurol. 2019;18(9):857–864.