Toni D, Frontoni M, Argentino C, Sacchetti M L, De Michele M, Fieschi C
Department of Neurological Sciences, University La Sapienza, Rome, Italy.
J Cardiovasc Pharmacol. 1991;18 Suppl 8:S10-4.
Clinical management of patients affected by subarachnoid hemorrhage has been modified by the use of nimodipine. Although no differences in overall neurologic outcome and rates of symptomatic spasm have been observed between nimodipine and control patients, severity of permanent neurologic deficits consequent to cerebral vasospasm is reduced in the former. On the other hand, clinical trials with nimodipine in ischemic stroke did not substantiate the expected neurologic benefits. A meta-analysis of the two phase IV studies published thus far shows that of 350 patients examined, mortality rate was 11.5% and 19% in subjects given nimodipine and placebo, respectively (n.s.). Cerebral death accounted for 30% of cases in both groups, whereas a lower percentage of cardiac and pulmonary fatal events were observed among nimodipine-treated subjects. Moreover, neurologic outcome of survivors was not significantly different. These results may be associated with the notion that the voltage-operated channel blockade exerted by calcium antagonists is only a part of the complex events leading to the enhancement of calcium ion intracellular concentration as a "common final pathway." However, difficulties encountered in planning clinical trials in acute ischemic stroke also might explain the lack of conclusive results. The feasibility of randomization of an adequate sample of patients and of very early therapeutic intervention after stroke onset are discussed.
尼莫地平的应用改变了蛛网膜下腔出血患者的临床管理。尽管在尼莫地平治疗组和对照组患者之间，未观察到总体神经功能结局和症状性痉挛发生率的差异，但前者因脑血管痉挛导致的永久性神经功能缺损的严重程度有所降低。另一方面，尼莫地平在缺血性卒中的临床试验并未证实预期的神经功能益处。对迄今为止发表的两项IV期研究的荟萃分析表明，在350例接受检查的患者中，服用尼莫地平和安慰剂的受试者的死亡率分别为11.5%和19%（无统计学差异）。两组中脑死亡均占病例的30%，而在接受尼莫地平治疗的受试者中，心脏和肺部致命事件的发生率较低。此外，幸存者的神经功能结局无显著差异。这些结果可能与以下观点有关，即钙拮抗剂所发挥的电压门控通道阻滞只是导致钙离子细胞内浓度升高这一“共同最终途径”的复杂事件的一部分。然而，急性缺血性卒中临床试验中遇到的困难也可能解释了为何缺乏确凿的结果。文中还讨论了对足够数量患者样本进行随机分组以及在卒中发作后进行极早期治疗干预的可行性。
