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[Correspondence] Intraparenchymal haemorrhages as a primary outcome measure

We read with interest the Article by Mikael Mazighi and colleagues,

1

  • Mazighi M
  • Richard S
  • Lapergue B
  • et al.

Safety and efficacy of intensive bloaod pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.

who tested whether an intensive blood pressure lowering regimen (target of 100–129 mm Hg systolic) after endovascular therapy resulted in lower rates of radiographic intraparenchymal haemorrhage at 24–36 h compared with the standard of care (130–185 mm Hg systolic) within the BP-TARGET trial. Mazighi and colleagues found no significant differences between the two groups in the primary outcome measure of intraparenchymal haemorrhage. We question the relevance of the primary outcome, because the definition of any intraparenchymal haemorrhage presumably included several small areas of bleeding typical of either petechial haemorrhage within an infarction or small confluent haemorrhage categorised as haemorrhagic infarction type 1 or 2, either of which usually involves small portions of the entire infarct extent.

2

  • von Kummer R
  • Broderick JP
  • Campbell BC
  • et al.

The Heidelberg Bleeding Classification: classification of bleeding events after ischemic stroke and reperfusion therapy.

The question of whether intensive blood pressure lowering can improve functional outcomes was not adequately powered for in the trial.

The use of a surrogate outcome as the primary outcome can be problematic, especially if it does not correlate well enough with conventional clinical outcomes, such as disability (eg, using the modified Rankin Scale). The presumed association of intraparenchymal haemorrhage with clinical outcome is based on several pathophysiological assumptions but, in most studies, only the more severe forms are associated with worse outcomes. In a post-hoc analysis of the ESCAPE-NA1 data, intracranial haemorrhage was not associated with worse outcome, after adjustment for baseline characteristics and infarct volume, and only the more severe space-occupying parenchymal haemorrhages (parenchymal haemorrhage type 1 or 2) were predictors of decreased functional outcome.

3

  • Ospel JM
  • Wu Q
  • Menon BK
  • et al.

Radiological patterns of intracranial hemorrhage and clinical outcome after endovascular treatment in acute ischemic stroke: results from the ESCAPE-NA1 Trial.

Similarly, a previous thrombolysis trial suggested that all haemorrhage severities, except haemorrhagic infarction type 1, predicted worse outcome.

4

  • Dzialowski I
  • Pexman JH
  • Barber PA
  • Demchuk AM
  • Buchan AM
  • Hill MD

Asymptomatic hemorrhage after thrombolysis may not be benign: prognosis by hemorrhage type in the Canadian alteplase for stroke effectiveness study registry.

In BP-TARGET, parenchymal haemorrhage type 2 made up only 15% of all radiographically confirmed intracranial bleeds, and parenchymal haemorrhage type 1 is not explicitly mentioned. More clarity in reporting the frequency of each haemorrhage grade (haemorrhagic infarction type 1 and 2 and parenchymal haemorrhage type 1 and 2) in both treatment groups would have been useful. The investigators appropriately powered the trial to detect a 15% difference when using any intraparenchymal haemorrhage as the outcome. However, a trial powered for a more clinically meaningful haemorrhage definition, such as parenchymal haemorrhage type 1 or type 2, would require a much larger sample size due to a much smaller expected difference.

In summary, we applaud the authors for their effort in the BP-TARGET trial. Although underpowered, similar outcomes with the modified Rankin Scale would suggest it is unnecessary to lower blood pressure after endovascular therapy reperfusion. We do question the choice of all intraparenchymal haemorrhages, including all types of haemorrhagic infarction, as the primary outcome, and would have preferred a more clinically meaningful, radiologically based haemorrhage surrogate outcome, such as parenchymal haemorrhage type 1 or type 2.

We declare no competing interests.

References

  1. 1.
    • Mazighi M
    • Richard S
    • Lapergue B
    • et al.

    Safety and efficacy of intensive bloaod pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.

    Lancet Neurol. 2021; 20 : 265-274
  2. 2.
    • von Kummer R
    • Broderick JP
    • Campbell BC
    • et al.

    The Heidelberg Bleeding Classification: classification of bleeding events after ischemic stroke and reperfusion therapy.

    Stroke. 2015; 46 : 2981-2986
  3. 3.
    • Ospel JM
    • Wu Q
    • Menon BK
    • et al.

    Radiological patterns of intracranial hemorrhage and clinical outcome after endovascular treatment in acute ischemic stroke: results from the ESCAPE-NA1 Trial.

    Radiology. 2021; ()
  4. 4.
    • Dzialowski I
    • Pexman JH
    • Barber PA
    • Demchuk AM
    • Buchan AM
    • Hill MD

    Asymptomatic hemorrhage after thrombolysis may not be benign: prognosis by hemorrhage type in the Canadian alteplase for stroke effectiveness study registry.

    Stroke. 2007; 38 : 75-79

Article Info

Publication History

Identification

DOI: https://doi.org/10.1016/S1474-4422(21)00183-6

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© 2021 Elsevier Ltd. All rights reserved.

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Linked Articles

  • Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial
    • An intensive systolic blood pressure target of 100–129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24–36 h as compared with a standard care systolic blood pressure target of 130–185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion.

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  • Intraparenchymal haemorrhages as a primary outcome measure – Authors' reply
    • We appreciate the interest of Mayank Goyal and colleagues regarding the BP-TARGET trial.1 Their main concern relates to the primary outcome, defined as all intraparenchymal haemorrhages.

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