Abstract 210: A Phase I Clinical Trial of Sildenafil for the Treatment of Cerebral Vasospasm Following Subarachnoid Hemorrhage
Introduction: Animal studies have indicated that phosophodiesterase V (PDE-V) inhibition reduces cerebral vasospasm and improves outcomes following subarachnoid hemorrhage (SAH).
Hypothesis: We hypothesize that sildenafil (an FDA-approved PDE-V inhibitor) is safe when given to patients with aneurysmal SAH and improves cerebral vasospasm.
Methods: A prospective, non-randomized proof-of-principle trial using a two-phase dose escalation scheme was implemented. Patients with SAH underwent day-7 screening angiography to assess for vasospasm. In phase I, those with moderate to severe vasospasm were given 10mg (low dose) of intravenous sildenafil, followed by repeat angiography 30 mins after infusion. In phase II, patients with any degree of vasospasm were given 30mg (high dose) of sildenafil, followed by repeat angiography.
Safety was assessed by analyzing vital signs, intracranial pressure (ICP) monitoring neurological status, and observing for the development of adverse reactions attributable to sildenafil.
Two blinded reviewers compared pre- and post-sildenafil angiographic images to admission angiography and subjectively graded them as “improvement” or “no improvement” in vasospasm. Unblinded quantitative measurements of vessel diameter change were also made between pre- and post-sildenafil angiograms.
Results: Eleven of 23 patients enrolled had vasospasm, received sildenafil and underwent repeat angiography (5 received the 10mg dose and 6 the 30mg dose).
There were no adverse effects upon heart rate, ICP, or neurologic status. Sildenafil infusion did result in a transient decline in mean arterial pressure (MAP). With the low dose there was a 16% decline in MAP with an average time to return to baseline of 16 mins. For the high dose the decline was 19% with an average of 33 mins to return to baseline.
Seven of 11 (64%) had angiographic improvement in vasospasm, with 3 of 5 (60%) from the low dose group and 4 of 6 (67%) from the high dose group. The average vessel dilatation in responders was 1.25 mm.
Conclusions: Sildenafil is safe and well tolerated when given for the acute treatment of SAH-related cerebral vasospasm. These findings provide preliminary evidence that angiograpic vasospasm is improved in select patients following sildenafil infusion.
Author Disclosures: C.W. Washington: Research Grant; Modest; NREF Research Grant. R. Dhar: None. C. Derdeyn: Expert Witness; Modest; Acute stroke diagnosis and treatment. Ownership Interest; Modest; Pulse Therapeutics. Consultant/Advisory Board; Modest; Penumbra, Inc, Microvention, Inc. Employment; Significant; U01 NS058728, NINDS SAMMPRIS NeuroInterventional co-PI. Honoraria; Significant; W.L. Gore and Associates. G. Zipfel: Research Grant; Modest; AHA, Pfizer, Barnes-Jewish Hospital Foundation, Hope Center for Neurological Disorders. Research Grant; Significant; NIH.
- © 2014 by American Heart Association, Inc.