Meta-Analysis of the Effectiveness and Safety of Prophylactic Use of Nimodipine in Patients with an Aneurysmal Subarachnoid Haemorrhage

Guang      Jian Liu; Jie      Luo; Li      Ping Zhang; Zheng      Jun Wang; Li      Li Xu; Guo      Hou He; Yan      Jun Zeng; Yun      Fu Wang

Abstract

Background and objectives: Cerebral vasospasm is an important cause of poor outcomes in subarachnoid haemorrhage patients. This study was designed to assess the effectiveness and safety of nimodipine in the prevention of cerebral vasospasm in aneurysmal subarachnoid haemorrhage patients.

Methods: We searched Pubmed, OVID, Embase, the Cochrane library, the stroke clinical trial registry, and the National Science and Technology Library database and collected prospective, randomised, controlled clinical trials of the prophylactic use of nimodipine for aneurismal subarachnoid haemorrhage patients. A meta-analysis was performed on the studies that met the criteria for inclusion.

Results: Eight studies met the inclusion criteria, and 1514 patients finished trial observation for the different indicators. Compared with the placebo group, fully recovered (all cases) patients increased 64% in the nimodipine group (P = 0.0002, OR = 1.64, 95% CI 1.26 – 2.13, NNT=-1.048), fully recovered or moderately disabled (all cases) patients increased 79% (P = 0.0007, OR = 1.79, 95% CI 1.28 – 2.51, NNT = -5.889), patient death (in cerebral vasospasm cases) decreased 74% (P = 0.008, OR = 0.26, 95% CI 0.09 – 0.71, NNT = 2.298), the incidence of symptomatic cerebral vasospasm decreased 46% (P < 0.00001, OR = 0.54, 95% CI 0.42 – 0.69, NNT = 1.952), the incidence of delayed neurological function deficits (all cases) decreased 38% (P < 0.0001, OR = 0.62, 95% CI 0.50 – 0.78, NNT = 1.078), the occurrence of cerebral infarction (on CT scan) decreased 58% (P = 0.001, OR = 0.58, 95% CI 0.42 – 0.81, NNT = 3.314), the occurrence of cerebral infarction (in cerebral vasospasm cases) decreased 65% (P = 0.003, OR = 0.35, 95% CI 0.17 – 0.69, NNT = 3.688), the occurrence of cerebral infarction (all cases) decreased 48% (P < 0.00001, OR = 0.52, 95% CI 0.41 – 0.66, NNT = 1.196), and the difference in recurrent haemorrhage and adverse reactions between the nimodipine and placebo groups was not statistically significant (nimodipine group versus placebo group, recurrent haemorrhage P = 0.15, OR = 0.75, 95% CI 0.50 – 1.11; adverse reaction P = 0.59, OR = 1.13, 95% CI 0.71 – 1.81).

Conclusion: Compared with placebo, nimodipine can significantly improve clinical outcomes, as assessed by self-formulated standards and Glasgow outcome scores, and it can significantly reduce the occurrence of symptomatic cerebral vasospasm and delayed neurological function deficits (all cases), as well as cerebral infarction, although the incidence rate of recurrent haemorrhage and adverse reactions is not significantly reduced by nimodipine.

Keywords: Nimodipine, Aneurysmal subarachnoid hemorrhage, Cerebral Vasospasm, Delayed neurological function deficits, clinical outcome, Meta-analysis, Cerebral Infarction, QUORUM, RCT