不同剂量阿替普酶治疗高龄患者急性脑梗死的临床效果比较

Clinical efficacy of different doses of alteplase in the treatment of acute cerebral infarction in older adult patients

目的比较不同剂量阿替普酶静脉溶栓治疗高龄急性脑梗死患者的临床疗效和安全性。方法收集2021年2月至2022年2月于温州市中心医院就诊的符合静脉溶栓指征的高龄急性脑梗死患者(发病在4.5 h内,年龄≥75岁)共65例,采用随机对照研究方法,以随机数字表法分为低剂量组(n=32,给予0.6 mg/kg的阿替普酶)、标准剂量组(n=33,给予0.9 mg/kg的阿替普酶静脉溶栓治疗)。观察比较两组患者治疗前及治疗后24 h、48 h美国国立卫生研究院卒中量表(NIHSS)评分、治疗前及治疗后7 d、14 d、90 d改良Rankin量表(MRS)评分,治疗前及治疗后24 h血清C反应蛋白(CRP)、神经元特异性烯醇化酶(NSE)、肿瘤坏死因子α(TNF-α)水平,治疗后24 h颅内出血、症状性颅内出血情况及治疗后90 d的病死率。结果与治疗前比较,两组患者治疗后24 h、48 h的NIHSS评分均显著降低(低剂量组:t_(24 h)=6.78,t_(48 h)=7.86;标准剂量组:t_(24 h)=8.09,t_(48 h)=10.13,均P<0.001),两组治疗后7 d、14 d、90 d的MRS评分均显著降低(低剂量组:t_(7 d)=5.19,t_(14 d)=8.47,t90 d=9.85;标准剂量组:t_(7 d)=6.83,t_(14 d)=7.74,t90 d=13.66,均P<0.001),两组治疗后24 h血清CRP、NSE、TNF-α水平均显著降低(低剂量组:t_(CRP)=5.13,t_(NSE)=4.22,t_(TNF-α)=34.29;标准剂量组:t_(CRP)=4.87,t_(NSE)=5.53,t_(TNF-α)=31.98,均P<0.001),差异均有统计学意义;治疗后同时间两组上述指标比较,差异均无统计学意义(均P>0.05)。与标准剂量组比较,低剂量组治疗后24 h颅内出血率降低,差异有统计学意义(χ2=4.58,P=0.032);而两组症状性颅内出血率、治疗后90 d的病死率比较,差异均无统计学意义(均P>0.05)。结论低剂量阿替普酶(0.6 mg/kg)静脉溶栓治疗高龄患者急性脑梗死的临床疗效与标准剂量(0.9 mg/kg)相当,而安全性更好。

Objective To investigate the clinical efficacy and safety of intravenous thrombolysis with different doses of alteplase in the treatment of acute cerebral infarction in older adult patients.Methods A total of 65 older adult patients with acute cerebral infarction(onset within 4.5 hours,age≥75 years)who underwent intravenous thrombolysis in Wenzhou Central Hospital from February 2021 to February 2022 were included in this study.They were randomly assigned to undergo intravenous thrombolysis with either low dose alteplase(0.6 mg/kg,low dose group,n=32)or standard dose alteplase(0.9 mg/kg,standard dose group,n=33).The National Institutes of Health Neurological Stroke Scale score before and 24 and 48 hours after treatment,modified Rankin scale score before and 7,14 and 90 days after treatment,serum C-reactive protein(CRP),neuron-specific enolase(NSE)and tumor necrosis factor-α(TNF-α)levels before and 24 hours after treatment,24-hour incidence of intracranial hemorrhage,24-hour incidence of symptomatic intracranial hemorrhage,and 90-day mortality were compared between the two groups.Results Compared with before treatment,the National Institutes of Health Neurological Stroke Scale scores in each group were significantly decreased at 24 and 48 hours after treatment(low dose group,t_(24 h)=6.78,t_(48 h)=7.86;standard dose group:t_(24 h)=8.09,t_(48 h)=10.13,all P<0.001).Compared with before treatment,the modified Rankin scale score in each group was significantly decreased at 7,14 and 90 days after treatment(low-dose group:t_(7 d)=5.19,t_(14 d)=8.47,t90 d=9.85;standard dose group:t_(7 d)=6.83,t_(14 d)=7.74,t90 d=13.66,all P<0.001).At 24 hours after treatment,serum levels of CRP,NSE,TNF-αin each group were significantly decreased(low-dose group:t_(CRP)=5.13,t_(NSE)=4.22,t_(TNF-α)=34.29;standard dose group:t_(CRP)=4.87,t_(NSE)=5.53,t_(TNF-α)=31.98,all P<0.001).At each time point after treatment,there were no significant differences in these indices between the two groups(all P>0.05).The 24-hour incidence of intracranial hemorrhage in the low dose group was significantly lower than that in the standard dose group(χ2=4.58,P=0.032).There were no significant differences in incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups(all P>0.05).Conclusion Intravenous thrombolysis with low dose alteplase(0.6 mg/kg)for the treatment of acute cerebral infarction in older adult patients exhibits equivalent clinical efficacy to that with standard dose alteplase(0.9 mg/kg),and the former is much safer than the latter.