Abstract 122: The P2x4 Inhibitor, Paroxetine Dramatically Prevents Not Only Growth Of Unruptured Cerebral Aneurysms But Also Recanalization After Aneurysm Coil Embolization; A Retrospective Clinical Study, Drug For Aneurysm Study

Abstract

Introduction: We have suggested that inhibition of P2X4 purinoceptor, which is involved in the endothelial flow sensing mechanism, prevents cerebral aneurysm development and growth in an animal model. Therefore, we retrospectively investigated whether a P2X4 inhibitor, paroxetine used as an antidepressant, has an inhibitory effect on the growth of unruptured cerebral aneurysms and the rate of recanalization after coil embolization. Methods: Among the cases registered in the J-ASPECT Study, the Japanese stroke inpatient reimbursement database, from 2010 to 2019, we searched for cases who were taking paroxetine and with registered unruptured cerebral aneurysm or had undergone cerebral aneurysm coil embolization. We then invited medical centers with these cases to participate in the study and enrolled cases that met the selection criteria by referring to the imaging data and patient background of the cases. The inhibitory effect in the paroxetine-treated group was compared with that of the control group in a multivariate analysis after adjustment for age, gender, and known risk factors. Results: There were 708 cases at 226 facilities nationwide that were potentially matched in the criteria. Seventy-four facilities participated, of which 74 cases at 45 facilities met the selection criteria. A total of 700 control cases were enrolled from 14 core participating centers. The rate of growth incidence of aneurysms was 0.0318 for paroxetine-treated cases (n=36) and 0.0960 for control cases (397). The significant factors (regression coefficients) were paroxetine (-2.26), specific sites of occurrence (-1.28), shape irregularity (1.63), age (0.11), female (1.54), hypertension (-0.55), statin (0.87), and family history of stroke (0.71). The significant factors (odds ratios) in recanalization after 1 year of coil embolization were paroxetine (0.21), complete embolization (0.26), ruptured aneurysm (3.95), and size (1.14). Conclusions: This retrospective study suggests that P2X4 inhibitors including paroxetine may be clinically applicable as agents to inhibit the growth of unruptured cerebral aneurysms and recanalization after 1 year of aneurysm coil embolization. The use of reimbursement information may be useful when collecting very rare cases.