Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older

ObjectiveWe sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan.MethodsWe analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3–6 at discharge) and mortality using multivariable analysis.ResultsThe elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%).Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2–1.7) despite a lower proportion of poor outcomes (0.84, 0.75–0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly.A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17–0.24), statin (0.63, 0.50–0.79), ozagrel sodium (0.72, 0.60–0.86), and cilostazol (0.63, 0.51–0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51–0.68), statin (0.84, 0.75–0.94), and EPA (0.83, 0.72–0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly.ConclusionsIn contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.

研究目的：本研究旨在探讨日本老年与非老年蛛网膜下腔出血（subarachnoid hemorrhage, SAH）患者中，脑血管痉挛治疗方式与药物对临床结局的影响是否存在差异。
研究方法：本研究分析了J-ASPECT研究诊断程序组合数据库（J-ASPECT Study Diagnosis Procedure Combination database），该数据集纳入2010至2014年间，来自579家医院、接受夹闭术或栓塞术的17343例患者。研究人员按年龄将患者分为两组：老年组（≥75岁，n=3885）与非老年组（n=13458）。采用多变量分析法，探究治疗方式与抗脑血管痉挛药物（盐酸法舒地尔、奥扎格雷钠、西洛他唑、他汀类药物、二十碳五烯酸（eicosapentaenoic acid, EPA）、依达拉奉）对院内不良结局（出院时改良Rankin量表（modified Rankin Scale, mRS）评分3~6分）及死亡率的影响。
研究结果：老年患者更常为女性，意识障碍与合并症发生率更高，且接受夹闭术与抗脑血管痉挛药物治疗的比例更低（奥扎格雷钠与他汀类药物除外）。老年患者院内死亡率与不良结局发生率均显著高于非老年患者（死亡率：15.8% vs. 8.5%；不良结局发生率：71.7% vs. 36.5%）。在非老年患者中，栓塞术虽可降低不良结局发生风险（比值比0.84，95%置信区间0.75~0.94），但与更高的死亡率相关（比值比1.43，95%置信区间1.2~1.7）；而老年患者中，治疗方式对临床结局无显著影响。盐酸法舒地尔（非老年组：0.20，95%置信区间0.17~0.24）、他汀类药物（0.63，0.50~0.79）、奥扎格雷钠（0.72，0.60~0.86）及西洛他唑（0.63，0.51~0.77）对死亡率的影响在老年与非老年患者中无显著差异。在非老年患者中，不良结局发生风险与盐酸法舒地尔（0.59，0.51~0.68）、他汀类药物（0.84，0.75~0.94）及二十碳五烯酸（0.83，0.72~0.94）的使用呈负相关；而老年患者中，上述药物对不良结局无显著影响。
研究结论：与非老年患者相比，老年患者的治疗方式对临床结局无显著影响。抗脑血管痉挛药物对死亡率的影响在老年与非老年患者中无显著差异，但对功能结局的影响则存在明显差异。