Effects of paroxetine, a P2X4 inhibitor, on cerebral aneurysm growth and recanalization after coil embolization: the NHO Drug for Aneurysm Study.

Autor:	Fukuda S; 1Department of Neurosurgery and., Niwa Y; 1Department of Neurosurgery and., Ren N; 2Next-Generational Research for Stroke and Heart Disease and., Yonemoto N; 3Department of Biostatistics, Faculty of Medicine, University of Toyama., Kasahara M; 4Institute for Clinical and Translational Science, Nara Medical University Hospital, Kashihara., Yasaka M; 5Department of Cerebrovascular Medicine and Neurology, National Hospital Organization Kyushu Medical Center, Fukuoka., Ezura M; 6Department of Neurosurgery, National Hospital Organization Sendai Medical Center, Sendai., Asai T; 7Department of Neurosurgery, National Hospital Organization Nagoya Medical Center, Nagoya., Miyazono M; 8Department of Neurosurgery, National Hospital Organization Ureshino Medical Center, Ureshino., Korai M; 9Department of Neurosurgery, National Hospital Organization Shikoku Medical Center for Children and Adults, Zentsuji., Tsutsumi K; 10Department of Neurosurgery, National Hospital Organization Nagasaki Medical Center, Omura., Shigeta K; 11Department of Neurosurgery, National Hospital Organization Disaster Medical Center, Tachikawa., Oi Y; 12Department of Neurosurgery, National Hospital Organization Maizuru Medical Center, Maizuru., Nishimura A; 13Department of Neurosurgery, School of Medicine, Graduate School of Medical Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka., Fukuda H; 14Department of Neurosurgery, Kochi Medical School Hospital, Nankoku., Goto M; 15Department of Neurosurgery, Kobe City Medical Center General Hospital, Kobe; and., Yoshida T; 16Department of Neurosurgery, Seijinkai Shimizu Hospital, Kyoto, Japan., Fukuda M; 1Department of Neurosurgery and., Yasoda A; 17Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto., Iihara K; 18Department of Neurosurgery, National Cerebral and Cardiovascular Center Hospital, Suita.
Jazyk:	angličtina
Zdroj:	Journal of neurosurgery [J Neurosurg] 2024 Oct 25, pp. 1-8. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.3171/2024.6.JNS24714
Abstrakt:	Objective: Rupture of cerebral aneurysms has a poor prognosis, and growing aneurysms are prone to rupture. Although the number of coil embolization procedures is increasing worldwide, they are more prone to recurrence than clipping surgeries. However, there is still no drug that prevents aneurysm growth or recanalization after coil embolization. The authors have previously focused on the role of hemodynamics in cerebral aneurysm development and reported that inhibition of the P2X4 purinoceptor, by which vascular endothelial cells sense blood flow, reduced the induction and growth of aneurysms in an animal model. In this study, the authors investigated the effects of paroxetine, a P2X4 inhibitor also used as an antidepressant, on aneurysm growth and recanalization after endovascular coiling. Methods: Using the J-ASPECT Study registry, the largest comprehensive reimbursement database system for acute stroke inpatient care in Japan, the authors searched for patients incidentally taking paroxetine who were registered in the decade 2010-2019 with an unruptured cerebral aneurysm or who underwent aneurysm coiling. They calculated the growth incidence and growth rate by the person-year method and the odds ratio for recanalization within 1 year after coiling and statistically compared to controls. Results: Seventy-eight stroke facilities participated, and 275 patients were identified as potentially eligible. Thirty-seven patients with unruptured aneurysms and 38 after coil embolization met all eligibility criteria. They were compared with 396 control cases of unruptured aneurysms and 308 coil-placement controls. Multivariate analysis showed that paroxetine significantly reduced the incidence of aneurysm growth (number of cases with growth/person/year; incidence rate ratio [IRR] 0.24, 95% CI 0.05-0.66; p = 0.003) and the growth rate (total increase in maximum diameter in millimeters/person/year; IRR 0.57, 95% CI 0.28-0.98; p = 0.04). Paroxetine also significantly reduced the odds of recanalization in the year after coiling (OR 0.21, 95% CI 0.05-0.95; p = 0.04). The authors then performed propensity score matching to reduce bias due to imbalances in patient characteristics between the two groups; the outcome confirmed that paroxetine significantly reduced aneurysm growth incidence (IRR 0.02, 95% CI 0.008-0.05; p < 0.0001) and growth rate (IRR 0.03, 95% CI 0.01-0.06; p < 0.0001) and the 1-year recanalization (OR 0.18, 95% CI 0.03-0.99; p = 0.04). Conclusions: This observational cohort study suggests that P2X4 inhibitors such as paroxetine may be clinically applicable as prophylaxis against aneurysm rupture and postoperative recanalization.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu