title: A prospective, multicenter, randomized study of the efficacy of eicosapentaenoic acid for cerebral vasospasm: the EVAS study.
abstract: OBJECTIVE
  The sphingosylphosphorylcholine-Rho-kinase pathway plays an important role in Ca(2+) sensitization of vascular smooth muscle contraction. Eicosapentaenoic acid (EPA) inhibits sphingosylphosphorylcholine -Rho-kinase-activated Ca(2+)-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.
authors.affiliation: Department of Neurosurgery and Clinical Neuroscience, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan; Department of Neurosurgery, Ootemachi Hospital, Kitakyushu, Fukuoka, Japan. Electronic address: h-yoneda@yamaguchi-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoneda
authors.affiliation: Department of Neurosurgery and Clinical Neuroscience, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shirao
authors.affiliation: Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Nakagawara
authors.affiliation: Department of Neurosurgery, Iwate Medical University, Morioka, Iwate, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ogasawara
authors.affiliation: Department of Neurosurgery, Kohnan Hospital, Sendai, Miyagi, Japan; Department of Neurosurgery, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
authors.affiliation: Department of Neurosurgery and Clinical Neuroscience, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D002317:Cardiovascular Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D015118:Eicosapentaenoic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000378:metabolism; D011446:Prospective Studies; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D002317:Cardiovascular Agents; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D054460:rho-Associated Kinases; D013110:Sphingosine