用盐皮质激素受体阻滞剂依普利酮治疗未破裂脑动脉瘤——初步研究

Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study.

作者信息

Nagahiro Shinji, Tada Yoshiteru, Satomi Junichiro, Kinouchi Tomoya, Kuwayama Kazuyuki, Yagi Kenji, Nakajima Kohei, Matsushita Nobuhisa, Miyamoto Takeshi, Yamaguchi Tadashi, Shimada Kenji, Korai Masaaki, Mure Hideo, Okayama Yoshihiro, Abe Takashi, Harada Masafumi, Kitazato Keiko T, Kanematsu Yasuhisa

机构信息

Department of Neurosurgery, Institute of Biomedical Biosciences, Tokushima University Graduate School, Tokushima, Japan.

出版信息

J Stroke Cerebrovasc Dis. 2018 Aug;27(8):2134-2140. doi: 10.1016/j.jstrokecerebrovasdis.2018.03.008. Epub 2018 Apr 2.

DOI:10.1016/j.jstrokecerebrovasdis.2018.03.008

PMID:29622372

Abstract

BACKGROUND

Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients.

METHODS

Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms.

RESULTS

Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%.

CONCLUSION

Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed.

摘要

背景

目前对于未破裂脑动脉瘤患者尚无药物治疗方法。我们在其他研究中表明，盐皮质激素受体拮抗剂依普利酮可预防去卵巢高血压动脉瘤大鼠模型中脑动脉瘤的形成。当前这项初步研究评估了依普利酮是否可用于预防高血压患者脑动脉瘤的生长和破裂。

方法

在2011年8月至2014年5月期间，我们在一项开放标签非对照临床试验中纳入了82例患有90个动脉瘤的患者。所有患者均事先提供了参与本研究的知情同意书，且均接受依普利酮治疗（25 - 100毫克/天）。我们研究的主要终点是脑动脉瘤的破裂和增大。

结果

82例患者中，80例（88个未破裂动脉瘤）接受了平均21.3个月的随访（动脉瘤年数为153.4）；12例患者（15.0%）永久停药。开始使用依普利酮后1个月及整个随访期间，依普利酮使血压保持在正常范围内。最值得注意的是，直径小于9毫米的动脉瘤无一破裂或增大。然而，2个大的血栓形成性动脉瘤中，1个增大，另1个破裂。总体年破裂率为0.65%；直径大于10毫米的动脉瘤年破裂率为13.16%；达到主要终点的总体年发生率为1.30%。