Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations

Alejandro N. SantosDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Laurèl RauschenbachDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Dino SabanDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Bixia ChenDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Annika LenkeitDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Hanah Hadice GullDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Christoph RießDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Cornelius DeuschlInstitute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen;

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Börge SchmidtInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen; and

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Ramazan JabbarliDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Karsten H. WredeDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Yuan ZhuDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Benedikt FrankDepartment of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, Germany

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Ulrich SureDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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Philipp DammannDepartment of Neurosurgery and Spine Surgery, University Hospital Essen;

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OBJECTIVE

The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM).

METHODS

The authors’ institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex.

RESULTS

Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03–1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%–29.38%) for the entire cohort, 31.41% (95% CI 23.26%–40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%–49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%–32.29%) for patients on statin medication, and 0% (95% CI 0%–30.13%) for patients on antithrombotic medication.

CONCLUSIONS

ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

ABBREVIATIONS

CCM = cerebral cavernous malformation; CRE = CCM-related epilepsy; DVA = developmental venous anomaly; FCCM = familial CCM; FU = follow-up; ICH = intracerebral hemorrhage.
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Illustration from Di Somma et al. (pp 1187–1190). Published with permission from Glia Media | Artist: Martha Headworth, MS.

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