A prospective, multicenter, randomized study of the efficacy of eicosapentaenoic acid for cerebral vasospasm: The EVAS study

Objective: The sphingosylphosphorylcholine-Rho-kinase pathway plays an important role in Ca²⁺ sensitization of vascular smooth muscle contraction. Eicosapentaenoic acid (EPA) inhibits sphingosylphosphorylcholine -Rho-kinase-activated Ca²⁺-sensitization in vitro and in subarachnoid hemorrhage (SAH) models in vivo and has also been shown to inhibit the occurrence of cerebral vasospasm (CIV) after the onset of SAH in a prospective, nonrandomized study. The current prospective, multicenter, randomized study was performed to confirm the preventive effects of EPA on CIV in patients with SAH. Methods: The trial population comprised 162 patients who underwent surgical clipping within 72 hours of the onset of SAH. Of these patients, 81 received 2700 mg/day EPA from the day after surgery until day 30 (EPA group), and 81 did not receive EPA (control group). The primary end point was the occurrence of symptomatic vasospasm (SV) or cerebral infarction caused by CIV. Results: The occurrences of SV (15% vs. 30%; P = 0.022) and CIV (7% vs. 21%; P = 0.012) were lower in the EPA group. Multivariate analysis revealed an adjusted odds ratio of 0.39 (95% confidence interval, 0.17-0.89; P = 0.028) for SV inhibition by EPA and 0.27 (95% confidence interval, 0.09-0.72; P = 0.012) for CIV inhibition. Conclusions: These results indicate that oral EPA reduces the frequency of SV and CIV after the onset of aneurysmal SAH.