University of Oulu

Räisänen, S, Huttunen, J, Huuskonen, TJ, et al. Risk factor management matters more than pharmaceutical cyclooxygenase-2 inhibition in the prevention of de novo intracranial aneurysms. Eur J Neurol. 2022; 29: 2734- 2743. doi: 10.1111/ene.15442

Risk factor management matters more than pharmaceutical cyclooxygenase-2 inhibition in the prevention of de novo intracranial aneurysms

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Author: Räisänen, Sari1,2,3; Huttunen, Jukka1,2; Huuskonen, Terhi J.1,2;
Organizations: 1Neurosurgery of NeuroCenter, Kuopio University Hospital, and Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
2Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland
3Hemorrhagic Brain Pathology Research Group, NeuroCenter, Kuopio University Hospital, Kuopio, Finland
4Neurosurgery at Neurocenter, University of Oulu and Oulu University Hospital, Oulu, Finland
5Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
6Faculty of Health Sciences, School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
7Department of Neurosurgery, Tampere University Hospital, Tampere, Finland
8Faculty of Medicine and Medical Technology, Tampere University, Tampere, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2022092059646
Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-06-09
Description:

Abstract

Background and purpose: Pathophysiological studies of saccular intracranial aneurysm (sIA) disease have shown that inflammation plays a crucial role in sIA development. Pharmaceutical inhibition of COX-2–PGE2–NF-κB signaling (COX-2, cyclooxygenase-2; PGE2, prostaglandin E2; NF-κB, nuclear factor κB) has been shown in animal models to inhibit sIA formation and progression suggesting that use of medication inhibiting COX-2 could reduce intracranial aneurysm formation also in patients.

Methods: The impact of COX-2 inhibition on de novo sIA formation was studied in two cohorts: in a previously described angiographically followed cohort of 1419 sIA patients and in a cohort of 117 sIA patients treated with stenting or stent-assisted embolization. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database. Data on the use of anti-inflammatory medications and hospital diagnoses were obtained from national registries. Risk factors were identified by univariate and multivariate analyses.

Results: De novo sIA patients were younger and more often smokers. Use of COX-2 selective inhibitors or nonsteroidal anti-inflammatory drugs did not significantly reduce de novo sIA formation, but the percentage of patients with de novo sIA formation was smaller in patients with prescribed regular acetylsalicylic acid medication (1.1% vs. 3.6%). In the multivariate analysis, however, neither acetylsalicylic acid use nor other type of pharmaceutical inhibition of COX-2 reduced the formation of de novo sIAs. The risk was mostly affected by age, smoking history and irregular usage of antihypertensive medication regardless of used COX-2 inhibition level.

Conclusions: For the prevention of de novo sIA formation, risk factor management with focus on cessation of smoking and treating hypertension adequately seems more important than pharmaceutical COX-2 inhibition.

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Series: European journal of neurology
ISSN: 1351-5101
ISSN-E: 1468-1331
ISSN-L: 1351-5101
Volume: 29
Issue: 9
Pages: 2734 - 2743
DOI: 10.1111/ene.15442
OADOI: https://oadoi.org/10.1111/ene.15442
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Subjects:
Funding: This study was funded by the Finnish Medical Foundation (PI Dr. Frösen), the Kuopio University Hospital, the Päivikki and Sakari Sohlberg Foundation, the Pro Humanitate Foundation, and the Academy of Finland.
Copyright information: This is the peer reviewed version of the following article: Räisänen, S, Huttunen, J, Huuskonen, TJ, et al. Risk factor management matters more than pharmaceutical cyclooxygenase-2 inhibition in the prevention of de novo intracranial aneurysms. Eur J Neurol. 2022; 29: 2734- 2743. doi: 10.1111/ene.15442, which has been published in final form at http://dx.doi.org/10.1111/ene.15442. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.