Abstract
Purpose
Cerebral vasospasm (CVS) is a frequent and unpredictable complication in patients with subarachnoid hemorrhage (SAH) and often leads to poor outcomes. This study was aimed at evaluating the efficacy and safety of fasudil in the treatment of CVS in patients with SAH.
Methods
A search was conducted using the full-text database of Chinese scientific journals, the Wanfang Database (January 1999 to November 2010), the Chinese Medical Association Digital Journal Database, PubMed, the Cochrane library, OVID, and EMBase (searching through November 2010).
Results
A total of 8 studies met the inclusion criteria. The incidence rates of symptomatic CVS and CVS confirmed by angiography among the patients in the fasudil group were only 48% (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.32–0.72, P = 0.0005) and 40% (OR = 0.40, 95% CI: 0.24-0–67, P = 0.0004) respectively of that of the control group. The odds ratios of cerebral infarction for all cases and cerebral infarction for CVS cases in the fasudil group were only 50% (OR = 0.50, 95% CI: 0.34–0.76, P = 0.0009) and 43% (OR = 0.43, 95% CI: 0.26–0.70, P = 0.0008) respectively of that of the control group.
Conclusions
Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients (as assessed by the Glasgow Outcome Scale). Because of the limited number of trials and samples available for analysis, the conclusions from the present study still need to be validated with results from large randomized, controlled clinical trials.
Similar content being viewed by others
References
Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Frey A, Marr A, Roux S, Kassell NF (2010) Preventing vasospasm improves outcome after aneurysmal subarachnoid hemorrhage: rationale and design of CONSCIOUS-2 and CONSCIOUS-3 trials. Neurocrit Care 13:416–424
Dorhout-Mees SM, Rinkel GJ, Feigin VL, Algra A, den Bergh WM v, Vermeulen M, van GJ (2007) Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev CD000277
Jang YG, Ilodigwe D, Macdonald RL (2009) Metaanalysis of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care 10:141–147
Kramer A, Fletcher J (2009) Do endothelin-receptor antagonists prevent delayed neurological deficits and poor outcomes after aneurysmal subarachnoid hemorrhage?: a meta-analysis. Stroke 40:3403–3406
Wang ZJ, Liu GJ (2011) Protection effect of endothelin receptor antagonist on blood vessel in patients with subarachnoid hemorrhage. China Pharm 22:525–529
Zhang S, Wang L, Liu M, Wu B (2010) Tirilazad for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2:CD006778
Zwienenberg-Lee M, Hartman J, Rudisill N, Madden LK, Smith K, Eskridge J, Newell D, Verweij B, Bullock MR, Baker A, Coplin W, Mericle R, Dai J, Rocke D, Muizelaar JP (2008) Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized, clinical trial. Stroke 39:1759–1765
Treggiari MM, Deem S (2009) Which H is the most important in triple-H therapy for cerebral vasospasm. Curr Opin Crit Care 15:83–86
Lohn M, Plettenburg O, Ivashchenko Y, Kannt A, Hofmeister A, Kadereit D, Schaefer M, Linz W, Kohlmann M, Herbert JM, Janiak P, O’Connor SE, Ruetten H (2009) Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension 54:676–683
Tiftik RN, Erol A, Cnar MG, Kubat H, Ark M, Ulker S, Buyukafsar K (2008) Nitric oxide does not down regulate Rho-kinase (ROCK-2) expression in rat coronary endothelial cells. J Cardiovasc Pharmacol 51:140–147
Yamaguchi S, Tanabe K, Takai S, Matsushima-Nishiwaki R, Adachi S, Iida H, Kozawa O, Dohi S (2009) Involvement of Rho-kinase in tumor necrosis factor-alpha-induced interleukin-6 release from C6 glioma cells. Neurochem Int 55:438–445
Satoh S, Hitomi A, Ikegaki I, Kawasaki K, Nakazono O, Iwasaki M, Mohri M, Asano T (2010) Amelioration of endothelial damage/dysfunction is a possible mechanism for the neuroprotective effects of Rho-kinase inhibitors against ischemic brain damage. Brain Res Bull 81:191–195
Li CH, Ye JY, Du P, Zhang QJ, Zhang GS, Sun GZ, Zhang JF, Li JH, Nie JG (2009) Effective evaluation of combined treatment in delayed cerebrovascular spasm after subarachnoid hemorrhage. J Apoplexy Nerv Dis 26:580–582
Nakashima S, Tabuchi K, Shimokawa S, Fukuyama K, Mineta T, Abe M (1998) Combination therapy of fasudil hydrochloride and ozagrel sodium for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo) 38:805–810; discussion 810–811
Shibuya M, Suzuki Y, Sugita K, Saito I, Sasaki T, Takakura K, Nagata I, Kikuchi H, Takemae T, Hidaka H, Nakashima M (1992) Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg 76:571–577
Ma JJ, Yang SY, Wei W, Yue SY, Zhong Y, Yang WD, Zhang DJ, Zhu SG, Zhu T, Li M, Yang YS, Li M, Shu BH, Zheng GE (2006) A phase clinical evaluation of fasudil hydrochloride for cerebral vasospasm following subarachnoid hemorrhage. Chin J Neurosurg 22:36–40
Tong HY, Yu XG, Xu BN (2002) The effects of a new vasodilator fasudil on delayed cerebral vasospasm after subarachnoid hemorrhage. Acad J PLA Postgrad Med Sch 23:53–56
Zhao JZ, Zhou DB, Guo J, Ren ZY, Zhou LF, Wang S, Xu BN, Wang RZ (2006) Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo) 46:421–428
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary. Control Clin Trials 17:1–12
Gao GC (2008) Effects of fasudil hydrochloride on cerebral vasospasm following subarachnoid hemorrhage. Chin J Misdiag 8:3844–3845
Ning L, Bo LH, Hong H (2008) Effect of fasodil on cerebral vasospasm in patients with subarachnoid hemorrhage. Chin J Pract Med 35:40–41
Hunt WE, Hess RM (1968) Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28:14–20
Hunt WE, Kosnik EJ (1974) Timing and perioperative care in intracranial aneurysm surgery. Clin Neurosurg 21:79–89
Jennett B, Bond MR (1975) Assessment of outcome after severe brain damage. Lancet 305:480–484
Teasdale G, Jennett B (1974) Assessment of coma and impaired consciousness. A practical scale. Lancet 304:81–84
Cao HJ, Liu JP (2010) [Number needed to treat (NNT), an index for clinical therapeutic efficacy assessment–its significance and application]. Chin J Integr Tradit West Med 30:752–756
Rosenthal R (1979) The “file drawer problem” and tolerance for null results. Psychol Bull 86:638–641
Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF (1999) Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 354:1896–1900
Acknowledgements
We are grateful to all the staff of American Journal Experts for language assistance and paper revision.
Conflict of interest
There was no conflict of interest among the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Liu, G.J., Wang, Z.J., Wang, Y.F. et al. Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage. Eur J Clin Pharmacol 68, 131–139 (2012). https://doi.org/10.1007/s00228-011-1100-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-011-1100-x