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Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial

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Abstract

Background

With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial.

Methods

We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110–139 mm Hg versus 140–179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days.

Results

Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00–5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71–1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions.

Conclusions

Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored.

Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565).

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Authors and Affiliations

  1. Division of Neurology, Department of Medicine, McMaster University / Population Health Research Institute, Hamilton, ON, Canada

    Ashkan Shoamanesh

  2. Department of Neurology J. P. Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

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

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

    Christy Cassarly & Renee H. Martin

  4. Stroke Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy

    Andrea Morotti

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

    Javier M. Romero

  6. Department of Neurology, University of South Wales, Sydney, Australia

    Kenneth Butcher

  7. Department of Neurology, Centre hospitalier de l’Université de Montréal (CHUM), Montréal, QC, Canada

    Laura Gioia

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

    Mohammad Rauf Afzal & Adnan I. Qureshi

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

    Jonathan Rosand & Joshua N. Goldstein

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

    Joshua N. Goldstein

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  1. Ashkan Shoamanesh
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Consortia

on behalf of the ATACH-2 and NETT investigators

Contributions

All authorship requirements have been met, and the final manuscript was approved by all authors. Study conception and design: AS, CC, AIQ, JR, JNG. Acquisition of data: AS, CC, AM, JR, JOF, FS, MJ, AA, AV, MRA, RHM. Administrative support: MJ, AA, AV, KS. Statistical analysis and interpretation of data: AS, CC, RHM, JR, JNG. Drafting of manuscript: AS. Critical revisions: AS, CC, AM, JR, JOF, FS, MJ, KB, LG, AA, AV, MRA, KS, MRA, RHM, AIQ, SMG, JR, JNG. Study supervision/funding: JNG, JR, AIQ.

Corresponding author

Correspondence to Ashkan Shoamanesh.

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Source of support

Supported by grants (National Institutes of Health - National Institute of Neurological Disorders and Stroke (NINDS) R01NS073344, to Dr. Rosand and U01-NS062091, to Dr. Qureshi). Chiesi USA and Astellas Pharma supplied intravenous nicardipine for use during the trial but had no other role in the design or conduct of the ATACH-2 trial or in this analysis/article. The National Institutes of Health, Chiesi USA, and Astellas Pharma had no involvement in the design, analyses, interpretation, or drafting of this report.

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval/informed consent

The ATACH-2 protocol and consent forms were approved by the institutional review board or equivalent ethics committee at each participating site, and all participants or their legally authorized representative provided written informed consent.

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Shoamanesh, A., Cassarly, C., Morotti, A. et al. Intensive Blood Pressure Lowering and DWI Lesions in Intracerebral Hemorrhage: Exploratory Analysis of the ATACH-2 Randomized Trial. Neurocrit Care 36, 71–81 (2022). https://doi.org/10.1007/s12028-021-01254-9

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