Effect of Statins on Neurological Functional Outcomes in Critically Ill Adult Patients with Traumatic Brain Injury: a Systematic Review and Meta-analysis

Overview

Journal BMJ Open

Specialty General Medicine

Date 2025 Feb 19

PMID 39971597

Authors

Charles Veillette

Mauricio Umana

Marc-Aurele Gagnon

Olivier Costerousse

Ryan Zarychanski

Daniel F McAuley

Patrick Lawler

Francois Lauzier

Shane W English

Lynne Moore

Chartelin Jean Isaac

Alexis F Turgeon

Affiliations

Soon will be listed here.

Abstract

Background: Statins are considered a promising therapy in traumatic brain injury (TBI) because of their role in mediating inflammatory injury and other endothelial properties. Whether they can improve patient outcomes is unknown.

Objectives: To evaluate the effect of statins in critically ill patients with TBI.

Design: Systematic review and meta-analysis of randomised controlled trials.

Eligibility Criteria: Trials of adult patients with acute moderate or severe TBI.

Methods: We searched Medline, Embase, Cochrane Central and Web of Science databases for trials comparing the use of any statin with placebo or other interventions. Our primary outcome was the Glasgow Outcome Scale (GOS or GOS extended); secondary outcomes were mortality, intensive care unit (ICU) and hospital length of stay. We used inverse variance random-effects models to calculate risk ratios (RR) and weighted mean differences. We assessed the risk of bias of trials using the Cochrane risk of bias assessment tool and the presence of statistical heterogeneity using the I index. Levels of evidence for summary effect measures were evaluated using Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: Of the 2418 retrieved records, 7 trials met our eligibility criteria. Three studied simvastatin, and four studied atorvastatin. The duration of the intervention ranged from 2 to 10 days, and outcomes were assessed between ICU discharge and 6 months. Five trials were considered at high risk of bias. We observed no statistically significant association between statins and the GOS (RR 0.42; 95% CI, 0.14 to 1.22; two trials; n=84, I=0%; very low certainty) or mortality (RR 0.59; 95% CI, 0.25 to 1.44; three trials; n=160, I=0%; very low certainty). No significant effect was observed for ICU length of stay, while hospital length of stay was evaluated in one trial showing shorter duration.

Conclusion: We found no conclusive evidence supporting the use of statins in critically ill adult patients with TBI at this time. Nevertheless, the trials were limited, and wide confidence intervals resulted in significant uncertainty of the findings. A potential benefit cannot be ruled out, underscoring the need for a larger, well-designed trial.

Prospero Registration Number: CRD42023421227.

References

Jeong S, Shin D, Yoo T, Cho M, Jang W, Lee J . Association between statin use and Alzheimer's disease with dose response relationship. Sci Rep. 2021; 11(1):15280. PMC: 8316580. DOI: 10.1038/s41598-021-94803-3. View

Bruns Jr J, Hauser W . The epidemiology of traumatic brain injury: a review. Epilepsia. 2003; 44(s10):2-10. DOI: 10.1046/j.1528-1157.44.s10.3.x. View

Dewan M, Rattani A, Gupta S, Baticulon R, Hung Y, Punchak M . Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018; 130(4):1080-1097. DOI: 10.3171/2017.10.JNS17352. View

Clay F, Hicks A, Zaman H, Ponsford J, Batty R, Perry L . Prophylaxis Pharmacotherapy to Prevent the Onset of Post-Traumatic Brain Injury Depression: A Systematic Review. J Neurotrauma. 2019; 36(13):2053-2064. DOI: 10.1089/neu.2018.6244. View

Turner G, McMullan C, Aiyegbusi O, Bem D, Marshall T, Calvert M . Stroke risk following traumatic brain injury: Systematic review and meta-analysis. Int J Stroke. 2021; 16(4):370-384. PMC: 8193616. DOI: 10.1177/17474930211004277. View

Li M, Huo X, Wang Y, Li W, Xiao L, Jiang Z . Effect of drug therapy on nerve repair of moderate-severe traumatic brain injury: A network meta-analysis. Front Pharmacol. 2022; 13:1021653. PMC: 9666493. DOI: 10.3389/fphar.2022.1021653. View

Kalra S, Malik R, Singh G, Bhatia S, Al-Harrasi A, Mohan S . Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation and anti-inflammatory drugs. Inflammopharmacology. 2022; 30(4):1153-1166. PMC: 9293826. DOI: 10.1007/s10787-022-01017-8. View

Wong S, Wilczynski N, Haynes R . Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. J Med Libr Assoc. 2006; 94(1):41-7. PMC: 1324770. View

Glanville J, Lefebvre C, Miles J, Camosso-Stefinovic J . How to identify randomized controlled trials in MEDLINE: ten years on. J Med Libr Assoc. 2006; 94(2):130-6. PMC: 1435857. View

10.

Jennett B, Snoek J, Bond M, Brooks N . Disability after severe head injury: observations on the use of the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry. 1981; 44(4):285-93. PMC: 490949. DOI: 10.1136/jnnp.44.4.285. View

11.

Grundy S, Stone N, Bailey A, Beam C, Birtcher K, Blumenthal R . 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; 139(25):e1082-e1143. PMC: 7403606. DOI: 10.1161/CIR.0000000000000625. View

12.

Wible E, Laskowitz D . Statins in traumatic brain injury. Neurotherapeutics. 2010; 7(1):62-73. PMC: 5084113. DOI: 10.1016/j.nurt.2009.11.003. View

13.

Wang H, Lynch J, Song P, Yang H, Yates R, Mace B . Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury. Exp Neurol. 2007; 206(1):59-69. DOI: 10.1016/j.expneurol.2007.03.031. View

14.

Morganti-Kossmann M, Satgunaseelan L, Bye N, Kossmann T . Modulation of immune response by head injury. Injury. 2007; 38(12):1392-400. DOI: 10.1016/j.injury.2007.10.005. View

15.

Naghibi T, Madani S, Mazloomzadeh S, Dobakhti F . Simvastatin's effects on survival and outcome in traumatic braininjury patients: a comparative study. Turk J Med Sci. 2016; 46(1):1-5. DOI: 10.3906/sag-1404-125. View

16.

Tramacere I, Boncoraglio G, Banzi R, Del Giovane C, Kwag K, Squizzato A . Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis. BMC Med. 2019; 17(1):67. PMC: 6436237. DOI: 10.1186/s12916-019-1298-5. View

17.

Luo D, Wan X, Liu J, Tong T . Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2016; 27(6):1785-1805. DOI: 10.1177/0962280216669183. View

18.

Farzanegan G, Derakhshan N, Khalili H, Ghaffarpasand F, Paydar S . Effects of atorvastatin on brain contusion volume and functional outcome of patients with moderate and severe traumatic brain injury; a randomized double-blind placebo-controlled clinical trial. J Clin Neurosci. 2017; 44:143-147. DOI: 10.1016/j.jocn.2017.06.010. View

19.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View

20.

Shen J, Shen J, Zhu K, Zhou H, Tian H, Yu G . Efficacy of Statins in Cerebral Vasospasm, Mortality, and Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. World Neurosurg. 2019; 131:e65-e73. DOI: 10.1016/j.wneu.2019.07.016. View