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Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial.
JAMA Neurol. 2018 07 01; 75(7):850-859.JN

Abstract

Importance

Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease.

Objectives

To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion.

Design, Setting, and Participants

Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses.

Main Outcomes and Measures

The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan.

Results

A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48).

Conclusions and Relevance

Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment.

Trial Registration

ClinicalTrials.gov Identifier: NCT01176565.

Authors+Show Affiliations

Division of Neurology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Stroke Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Mondino Foundation, Pavia, Italy.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.Zeenat Qureshi Stroke Research Center, University of Minnesota, Minneapolis.Department of Public Health Sciences, Medical University of South Carolina, Charleston.Department of Public Health Sciences, Medical University of South Carolina, Charleston.Zeenat Qureshi Stroke Research Center, University of Minnesota, Minneapolis.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston.No affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29710119

Citation

Shoamanesh, Ashkan, et al. "Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction On Hematoma Expansion and Functional Outcomes: a Secondary Analysis of the ATACH-2 Randomized Clinical Trial." JAMA Neurology, vol. 75, no. 7, 2018, pp. 850-859.
Shoamanesh A, Morotti A, Romero JM, et al. Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial. JAMA Neurol. 2018;75(7):850-859.
Shoamanesh, A., Morotti, A., Romero, J. M., Oliveira-Filho, J., Schlunk, F., Jessel, M. J., Ayres, A. M., Vashkevich, A., Schwab, K., Afzal, M. R., Cassarly, C., Martin, R. H., Qureshi, A. I., Greenberg, S. M., Rosand, J., & Goldstein, J. N. (2018). Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial. JAMA Neurology, 75(7), 850-859. https://doi.org/10.1001/jamaneurol.2018.0454
Shoamanesh A, et al. Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction On Hematoma Expansion and Functional Outcomes: a Secondary Analysis of the ATACH-2 Randomized Clinical Trial. JAMA Neurol. 2018 07 1;75(7):850-859. PubMed PMID: 29710119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial. AU - Shoamanesh,Ashkan, AU - Morotti,Andrea, AU - Romero,Javier M, AU - Oliveira-Filho,Jamary, AU - Schlunk,Frieder, AU - Jessel,Michael J, AU - Ayres,Alison M, AU - Vashkevich,Anastasia, AU - Schwab,Kristin, AU - Afzal,Mohammad R, AU - Cassarly,Christy, AU - Martin,Renee H, AU - Qureshi,Adnan I, AU - Greenberg,Steven M, AU - Rosand,Jonathan, AU - Goldstein,Joshua N, AU - ,, PY - 2018/5/2/pubmed PY - 2019/10/23/medline PY - 2018/5/1/entrez SP - 850 EP - 859 JF - JAMA neurology JO - JAMA Neurol VL - 75 IS - 7 N2 - Importance: Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease. Objectives: To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion. Design, Setting, and Participants: Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses. Main Outcomes and Measures: The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan. Results: A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48). Conclusions and Relevance: Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01176565. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/29710119/Cerebral_Microbleeds_and_the_Effect_of_Intensive_Blood_Pressure_Reduction_on_Hematoma_Expansion_and_Functional_Outcomes:_A_Secondary_Analysis_of_the_ATACH_2_Randomized_Clinical_Trial_ DB - PRIME DP - Unbound Medicine ER -