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White Matter Hyperintensities and Blood Pressure Lowering in Acute Intracerebral Hemorrhage: A Secondary Analysis of the ATACH-2 Trial

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Abstract

Background

It is not clear whether subsets of patients with intracerebral hemorrhage (ICH) benefit from intensive blood pressure (BP) lowering. We evaluated whether white matter hyperintensities (WMH) burden influences response to this therapy.

Methods

Retrospective secondary analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Patients were randomized to intensive (systolic BP target: 110–139 mmHg) versus standard (systolic BP target: 140–179 mmHg) BP treatment with intravenous nicardipine within 4.5 h from onset between May 2011 and September 2015. WMH were rated on magnetic resonance images (fluid-attenuated inversion recovery sequences), defining moderate–severe WMH as total Fazekas scale score ≥ 3 (range 0–6). The main outcome was death or major disability at 90 days (modified Rankin scale ≥ 3). The secondary outcome was ICH expansion, defined as hematoma growth > 33% from baseline to follow-up CT scan. Predictors of the outcomes of interest were explored with multivariable logistic regression.

Results

A total of 195/1000 patients had MRI images available for analysis, of whom 161 (82.6%) had moderate–severe WMH. When compared to patients with none–mild WMH, those with moderate–severe WMH did not have an increased risk of death or major disability (adjusted relative risk: 1.83, 95% CI 0.71–4.69) or ICH expansion (adjusted relative risk: 1.14, 95% CI 0.38–3.37). WMH burden did not modify the effect of intensive BP treatment on outcome (all p for interaction ≥ 0.2).

Conclusion

The majority of acute ICH patients have moderate–severe WMH, but advanced small vessel disease burden marked by WMH does not influence ICH-related outcomes or response to intensive BP reduction.

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Funding

The present study was supported by the following awards from the National Institute of Neurological Disorders and Stroke: 5R01NS073344. The funding source did not have any involvement in study design; data collection, analysis and interpretation; writing of the manuscript; or decision to submit the study for publication.

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Author notes

  1. Andrea Morotti and Ashkan Shoamanesh have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Neurorehabilitation, IRCCS Mondino Foundation, Via Mondino 2, 27100, Pavia, Italy

    Andrea Morotti

  2. Population Health Research Institute, McMaster University, Hamilton, ON, Canada

    Ashkan Shoamanesh

  3. J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Jamary Oliveira-Filho, Frieder Schlunk, Michael Jessel, Alison Ayres, Anastasia Vashkevich, Kristin Schwab, Steven M. Greenberg, Jonathan Rosand & Joshua N. Goldstein

  4. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Javier M. Romero

  5. Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Jonathan Rosand & Joshua N. Goldstein

  6. Henry and Allison Center for Brain Health, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Jonathan Rosand

  7. Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Jonathan Rosand

  8. Zeenat Qureshi Stroke Research Center, University of Minnesota, Minneapolis, USA

    Adnan I. Qureshi

  9. Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA

    Christy Cassarly & Renee’ Hebert Martin

  10. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Joshua N. Goldstein

Authors
  1. Andrea Morotti
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  2. Ashkan Shoamanesh
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  3. Jamary Oliveira-Filho
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  8. Anastasia Vashkevich
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  9. Kristin Schwab
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  10. Christy Cassarly
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  11. Renee’ Hebert Martin
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  12. Steven M. Greenberg
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  13. Adnan I. Qureshi
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  14. Jonathan Rosand
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  15. Joshua N. Goldstein
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Consortia

Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) and the Neurological Emergencies Treatment Trials (NETT) Network Investigators

Contributions

AS, JR and JNG contributed to study concept and design. All authors contributed to acquisition of data. AS, AM, JO-F, FS and JMR contributed to imaging analysis. CC and RHM contributed to statistical analysis. All authors analyzed and interpreted the data. AM, AS and JNG drafted the manuscript. All authors critically revised the manuscript for important intellectual content. JR and JNG obtained funding. JR and JNG supervised the study.

Corresponding author

Correspondence to Andrea Morotti.

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Conflict of interest

Andrea Morotti reports no disclosures. Ashkan Shoamanesh reports research funding from Bristol-Myer Squibb, Bayer AG and Servier Canada Inc., and consulting from Apopharma Inc., Bayer AG, Daiichi Sankyo, Servier Canada Inc., Bristol-Myer Squibb and Boehringer Ingelheim. Jamary Oliveira-Filho reports no disclosures. Frieder Schlunk reports no disclosures. Javier M. Romero reports no disclosures. Michael Jessel reports no disclosures. Alison Ayres reports no disclosures. Anastasia Vashkevich reports no disclosures. Kristin Schwab reports no disclosures. Christy Cassarly reports no disclosures. Renee’ Hebert Martin reports no disclosures. Steven M. Greenberg reports no disclosures. Adnan I. Qureshi reports no disclosures. Jonathan Rosand reports consulting for Pfizer, Boehringer Ingelheim. Joshua Goldstein reports research funding from Pfizer, Portola, and consulting from CSL Behring, Octapharma, Phillips.

Ethical Approval/Informed Consent

Local Institutional Review Boards approval was obtained at all ATACH-2 enrolling sites, and informed consent was obtained from all participants.

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Table 1 and list of ATACH-2 and NETT investigators (DOC 128 kb)

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Morotti, A., Shoamanesh, A., Oliveira-Filho, J. et al. White Matter Hyperintensities and Blood Pressure Lowering in Acute Intracerebral Hemorrhage: A Secondary Analysis of the ATACH-2 Trial. Neurocrit Care 32, 180–186 (2020). https://doi.org/10.1007/s12028-019-00761-0

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  • DOI: https://doi.org/10.1007/s12028-019-00761-0

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