Abstract TP90: A Pilot Study of the Mineralocorticoid Receptor Blocker Eplerenone in Hypertensive Patients with Unruptured Cerebral Aneurysms

Abstract

Background: 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 ovariectomized rats. This pilot study was designed to evaluate whether it can be used to prevent the growth and rupture of cerebral aneurysms in humans with hypertension. Methods: Between August 2011 and May 2014, 82 patients with 89 aneurysms were enrolled in an open-label uncontrolled clinical trial. Of these, 81 patients (88 unruptured aneurysms) were followed for a mean of 21.2 months (153.7 aneurysm-years). All patients had a history of hypertension and were treated with eplerenone (20 - 100 mg per day). The primary endpoints were rupture and enlargement of the intracranial aneurysms. Results: The mean aneurysmal size was 4.6 ± 2.6 mm. During follow-up period that included 153.7 aneurysm-years, 3 aneurysms enlarged and one large thrombosed aneurysm rupture. The annual rupture was 0.65% overall and 13.16% for aneurysms larger than 10 mm. No aneurysms smaller than 9 mm ruptured. The annual rate for reaching the primary endpoint was 2.60% overall. It was 1.37% for aneurysms smaller than 9 mm and thus seems to be lower than in other studies. Eplerenone had no protective effects in aneurysms larger than 10 mm. In the course of our study, 12 patients (14.8%) permanently discontinued taking the eplerenone. Conclusions: Our observations suggest that it is clinically feasible to prevent growth and rupture of cerebral aneurysms smaller than 9 mm by treatment with eplerenone. Protocols for large clinical trial are needed to assess the possible long-term clinical benefits the drug may confer on patients with unruptured cerebral aneurysms.