Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury

  • Joshua S. Catapano
  • Alistair J. Chapman
  • Matthew Dull
  • Joseph M. Abbatematteo
  • Lance P. Horner
  • Jakub Godzik
  • Scott Brigeman
  • Clinton D. Morgan
  • Alexander C. Whiting
  • Minggen Lu
  • Joseph M. ZabramskiEmail author
  • Douglas R. Fraser
Original Work



Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting. β-blockers (BBs), however, appear to be associated with reduced mortality among patients with isolated TBI.


Examine the association between preinjury ACEI and BB use and clinical outcome among patients with isolated TBI.


A retrospective cohort study of patients age ≥ 40 years admitted to an academic level 1 trauma center with isolated TBI between January 2010 and December 2014 was performed. Isolated TBI was defined as a head Abbreviated Injury Scale (AIS) score ≥ 3, with chest, abdomen, and extremity AIS scores ≤ 2. Preinjury medication use was determined through chart review. All patients with concurrent BB use were initially excluded. In-hospital mortality was the primary measured outcome.


Over the 5-year study period, 600 patients were identified with isolated TBI who were naive to BB use. There was significantly higher mortality (P = .04) among patients who received ACEI before injury (10 of 96; 10%) than among those who did not (25 of 504; 5%). A multivariate stepwise logistic regression analysis revealed a threefold increased risk of mortality in the ACEI cohort (P < .001), which was even greater than the twofold increased risk of mortality associated with an Injury Severity Score ≥ 16. A second analysis that included patients who received preinjury BBs (n = 98) demonstrated slightly reduced mortality in the ACEI cohort with only a twofold increased risk in multivariate analysis (P = .05).


Preinjury exposure to ACEIs is associated with an increase in mortality among patients with isolated TBI. This effect is ameliorated in patients who receive BBs, which provides evidence that this class of medications may provide a protective benefit.


Angiotensin-converting enzyme inhibitor β-Blockers Isolated Mortality Traumatic brain injury 



Angiotensin-converting enzyme inhibitor


Abbreviated Injury Scale




Glasgow Coma Scale


Injury Severity Score


Odds ratio


Systolic blood pressure


Traumatic brain injury



The authors thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation.

Author Contributions

JSC performed data collection or management, data analysis, protocol/project development, and manuscript writing/editing. AJC contributed to protocol/project development and manuscript writing/editing. MD, JMA, JG, SB, CDM, and ACW performed manuscript writing/editing. LPH was involved in data collection or management. ML was involved in data analysis. JMZ performed manuscript writing/editing/approval. DRF performed protocol/project development and manuscript writing/editing. The authors confirm that authorship requirements have been met and the final manuscript was approved by all authors.

Source of Support

There was no support for this work.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was waived on IRB approval and was not obtained because of the retrospective nature of the study with minimal risk to patients.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  • Joshua S. Catapano
    • 1
  • Alistair J. Chapman
    • 2
  • Matthew Dull
    • 2
  • Joseph M. Abbatematteo
    • 1
  • Lance P. Horner
    • 3
  • Jakub Godzik
    • 1
  • Scott Brigeman
    • 1
  • Clinton D. Morgan
    • 1
  • Alexander C. Whiting
    • 1
  • Minggen Lu
    • 4
  • Joseph M. Zabramski
    • 1
    Email author
  • Douglas R. Fraser
    • 3
  1. 1.Department of Neurosurgery, Barrow Neurological InstituteSt. Joseph’s Hospital and Medical CenterPhoenixUSA
  2. 2.Spectrum Health Hospital, Acute Care SurgeryMichigan State University College of Human MedicineGrand RapidsUSA
  3. 3.Department of SurgeryUniversity of Nevada Las Vegas School of MedicineLas VegasUSA
  4. 4.Department of Community Health SciencesUniversity of Nevada, RenoRenoUSA

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