轻型急性缺血性卒中rt-PA静脉溶栓的疗效和安全性研究
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摘要
目的探讨轻型急性缺血性卒中rt-PA静脉溶栓的疗效和安全性及预后不良的危险因素。方法前瞻性分析从2016年1月～2018年5月在深圳市6个卒中中心接受rt-PA静脉溶栓的急性缺血性卒中患者临床资料共224例,将美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)≤5分定义为轻型卒中(minor stroke,MS),共116例,NIHSS> 5分为非轻型卒中(non-minor stroke,NMS),共108例。比较两组基线资料、两组治疗后90 d改良Rankin评分(mRS)、治疗后7 d内症状性颅内出血(symptomatic intracerebral hemorrhage,s ICH)及早期神经功能恶化(early neurological deterioration,END)发生率、90 d死亡率的差异。运用单因素及多因素logistic回归分析探讨影响rt-PA静脉溶栓的MS患者预后不良的危险因素。结果两组基线资料中,与NMS组相比,MS组心源性栓塞型卒中比例更低(7. 8%vs 17. 6%,P=0. 026),而小动脉闭塞型卒中比例明显更高(41. 4%vs24. 1%,P=0. 006)。疗效性上,MS组90 d预后良好(mRS≤2分)比例明显高于NMS组(87. 9%vs 63%,OR6. 099,95%CI 2. 650～14. 040,P <0. 001)。安全性上,MS组7 d内END发生率高于NMS组(5. 2%vs 4. 6%); 7 d内s ICH发生率低于NMS组(4. 3%vs 6. 5%); 90 d内死亡率低于NMS组(1. 7%vs 7. 4%),校正前后差异均无统计学意义。单因素Logistic回归分析提示即使接受静脉溶栓治疗,大动脉粥样硬化型卒中、END、既往缺血性脑卒中病史、既往接受抗血小板治疗与MS患者预后不良相关,而多因素logistic回归分析提示只有END与预后不良相关。结论与NMS相比,MS患者接受rt-PA静脉溶栓有助于改善90 d的神经功能预后,安全性与NMS相似。即使接受rt-PA静脉溶栓治疗,END仍然是MS患者预后不良的独立危险因素。
Objective To explore the efficacy and safety of intravenous thrombolysis with rt-PA for mild acute ischemic stroke,and the risk factors of poor prognosis in these patients. Methods From January 2016 to May 2018,we prospectively analysed analyzed 224 patients with acute ischemic stroke received intravenous thrombolysis with rt-PA in 6 stroke centers in Shenzhen,minor stroke( MS) was defined as National Institutes of Health Stroke Scale( NIHSS) ≤5,including 116 patients,non-minor stroke( NMS) was defined as NIHSS > 5,including 108 patients. The baseline data,the modified Rankin scale( mRS) in the 90-day,the rate of symptomatic intracerebral hemorrhage( s ICH) and early neurological deterioration( END) during 7 days after treatment,the mortality in the 90-day between the two groups were compared. Univariate and multivariate logistic regression analysis was used to explore the risk factors of poor prognosis in MS patients treated with rt-PA. Results Compared with NMS,the proportion of cardiogenic embolism stroke in MS was significantly lower( 7. 8% vs17. 6%,P = 0. 026),while the proportion of small artery occlusive stroke was significantly higher( 41. 4% vs 24. 1%,P =0. 006). In efficacy,the proportion of the good outcome in the 90-day( mRS≤2) in MS group was obviously significantly higher than that in NMS group( 87. 9% vs 63%,OR 6. 099,95% CI 2. 650 ～ 14. 040,P < 0. 001). In safety,compared with NMS,the rate of END was higher( 5. 2% vs 4. 6%),the rate of s ICH was lower( 4. 3% vs 6. 5%),the mortality in the 90-day was lower( 1. 7% vs 7. 4%) in the MS group,there was no significant difference before and after correcting confounding factors. In Univariate logistic regression analysis,even received rt-PA,large artery atherosclerotic stroke,END,previous history of ischemic stroke and previous antiplatelet therapy were associated with poor prognosis in MS patients,while in multivariate logistic regression analysis,only END was associated with poor prognosis. Conclusion Compared with NMS,intravenous thrombolysis with rt-PA for MS patients can improve the 90-day neurological function,the safety is similar as NMS.Even received rt-PA,END is still an independent risk factor for poor prognosis in MS patients.
Objective To explore the efficacy and safety of intravenous thrombolysis with rt-PA for mild acute ischemic stroke,and the risk factors of poor prognosis in these patients. Methods From January 2016 to May 2018,we prospectively analysed analyzed 224 patients with acute ischemic stroke received intravenous thrombolysis with rt-PA in 6 stroke centers in Shenzhen,minor stroke( MS) was defined as National Institutes of Health Stroke Scale( NIHSS) ≤5,including 116 patients,non-minor stroke( NMS) was defined as NIHSS > 5,including 108 patients. The baseline data,the modified Rankin scale( mRS) in the 90-day,the rate of symptomatic intracerebral hemorrhage( s ICH) and early neurological deterioration( END) during 7 days after treatment,the mortality in the 90-day between the two groups were compared. Univariate and multivariate logistic regression analysis was used to explore the risk factors of poor prognosis in MS patients treated with rt-PA. Results Compared with NMS,the proportion of cardiogenic embolism stroke in MS was significantly lower( 7. 8% vs17. 6%,P = 0. 026),while the proportion of small artery occlusive stroke was significantly higher( 41. 4% vs 24. 1%,P =0. 006). In efficacy,the proportion of the good outcome in the 90-day( mRS≤2) in MS group was obviously significantly higher than that in NMS group( 87. 9% vs 63%,OR 6. 099,95% CI 2. 650 ～ 14. 040,P < 0. 001). In safety,compared with NMS,the rate of END was higher( 5. 2% vs 4. 6%),the rate of s ICH was lower( 4. 3% vs 6. 5%),the mortality in the 90-day was lower( 1. 7% vs 7. 4%) in the MS group,there was no significant difference before and after correcting confounding factors. In Univariate logistic regression analysis,even received rt-PA,large artery atherosclerotic stroke,END,previous history of ischemic stroke and previous antiplatelet therapy were associated with poor prognosis in MS patients,while in multivariate logistic regression analysis,only END was associated with poor prognosis. Conclusion Compared with NMS,intravenous thrombolysis with rt-PA for MS patients can improve the 90-day neurological function,the safety is similar as NMS.Even received rt-PA,END is still an independent risk factor for poor prognosis in MS patients.
引文
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[3]Kim DH,Lee DS,Nah HW,et al. Clinical and radiological factors associated with unfavorable outcome after intravenous thrombolysis in patients with mild ischemic stroke[J]. BMC Neurol,2018,18(1):30.
[4]Khatri P,Kleindorfer DO,Devlin T,et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits:the PRISMS randomized clinical trial[J]. JAMA,2018,320(2):156-166.
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[6]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51(9):666-682.
[7]Powers WJ,Rabinstein AA,Ackerson T,et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke:A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association[J]. Stroke,2018,49(3):e46-e110.
[8]Khatri P,Conaway MR,Johnston KC. Ninety-day outcome rates of a prospective cohort of consecutive patients with mild ischemic stroke[J]. Stroke,2012,43(2):560-562.
[9]Ali SF,Siddiqui K,Ay H,et al. Baseline predictors of poor outcome in patients too good to treat with intravenous thrombolysis[J]. Stroke,2016,47(12):2986-2992.
[10]Kim JT,Park MS,Choi KH,et al. Clinical outcomes of posterior versus anterior circulation infarction with low National Institutes of Health stroke scale scores[J]. Stroke,2017,48(1):55-62.
[11]Emberson J,Lees KR,Lyden P,et al. Effect of treatment delay,age,and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke:a meta-analysis of individual patient data from randomised trials[J]. Lancet,2014,384(9958):1929-1935.
[12]Greisenegger S,Seyfang L,Kiechl S,et al. Thrombolysis in patients with mild stroke:results from the Austrian Stroke Unit Registry[J].Stroke,2014,45(3):765-769.
[13]Laurencin C,Philippeau F,Blanc-Lasserre K,et al. Thrombolysis for acute minor stroke:outcome and barriers to management. Results from the RESUVAL stroke network[J]. Cerebrovasc Dis,2015,40(1/2):3-9.
[14]Khatri P,Kleindorfer DO,Yeatts SD,et al. Strokes with minor symptoms:an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials[J]. Stroke,2010,41(11):2581-2586.
[15]Spokoyny I,Raman R,Ernstrom K,et al. Defining mild stroke:outcomes analysis of treated and untreated mild stroke patients[J]. J Stroke Cerebrovasc Dis,2015,24(6):1276-1281.
[16]Romano JG,Smith EE,Liang L,et al. Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis:a retrospective analysis of the Get With the Guidelines-Stroke registry[J]. JAMA Neurol,2015,72(4):423-431.
[17]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2014[J].中华神经科杂志,2015,48(4):246-257.
[18]Hacke W,Kaste M,Bluhmki E,et al. Thrombolysis with alteplase 3to 4. 5 hours after acute ischemic stroke[J]. N Engl J Med,2008,359(13):1317-1329.
[19]Khatri P,Tayama D,Cohen G,et al. Effect of intravenous recombinant tissue-type plasminogen activator in patients with mild stroke in the third international stroke trial-3:post hoc analysis[J]. Stroke,2015,46(8):2325-2327.
[20]Yang J,Yu F,Liu H,et al. A Retrospective study of thrombolysis with 0. 6 mg/kg recombinant tissue plasminogen activator(rt-PA)in mild stroke[J]. Sci Rep,2016,6(8):31344.
[21]Ng FC,Coote S,Frost T,et al. Utility of computed tomographic perfusion in thrombolysis for minor stroke[J]. Stroke,2016,47(7):1914-1916.
[22]Seners P,Turc G,Tisserand M,et al. Unexplained early neurological deterioration after intravenous thrombolysis:incidence,predictors,and associated factors[J]. Stroke,2014,45(7):2004-2009.
[23]Smith EE,Abdullah AR,Petkovska I,et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke[J]. Stroke,2005,36(11):2497-2499.
[24]Rajajee V,Kidwell C,Starkman S,et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke[J]. Neurology,2006,67(6):980-984.
[25]Willey JZ,Stillman J,Rivolta JA,et al. Too good to treat? Outcomes in patients not receiving thrombolysis due to mild deficits or rapidly improving symptoms[J]. Int J Stroke,2012,7(3):202-206.
[26]Strbian D,Piironen K,Meretoja A,et al. Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms[J].Int J Stroke,2013,8(5):293-299.
[27]Khrmann M,Nowe T,Huttner HB,et al. Safety and outcome after thrombolysis in stroke patients with mild symptoms[J]. Cerebrovasc Dis,2009,27(2):160-166.
[28]Hao Z,Liu M,Wang D,et al. Etiologic subtype predicts outcome in mild stroke:prospective data from a hospital stroke registry[J]. BMC Neurol,2013,13(10):154.
[2]Chen W,Pan Y,Zhao X,et al. Intravenous thrombolysis in Chinese patients with different subtype of mild stroke:thrombolysis in patients with mild stroke[J]. Sci Rep,2017,7(1):2299.
[3]Kim DH,Lee DS,Nah HW,et al. Clinical and radiological factors associated with unfavorable outcome after intravenous thrombolysis in patients with mild ischemic stroke[J]. BMC Neurol,2018,18(1):30.
[4]Khatri P,Kleindorfer DO,Devlin T,et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits:the PRISMS randomized clinical trial[J]. JAMA,2018,320(2):156-166.
[5]Reeves M,Khoury J,Alwell K,et al. Distribution of National Institutes of Health stroke scale in the Cincinnati/Northern Kentucky Stroke Study[J]. Stroke,2013,44(11):3211-3213.
[6]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2018[J].中华神经科杂志,2018,51(9):666-682.
[7]Powers WJ,Rabinstein AA,Ackerson T,et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke:A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association[J]. Stroke,2018,49(3):e46-e110.
[8]Khatri P,Conaway MR,Johnston KC. Ninety-day outcome rates of a prospective cohort of consecutive patients with mild ischemic stroke[J]. Stroke,2012,43(2):560-562.
[9]Ali SF,Siddiqui K,Ay H,et al. Baseline predictors of poor outcome in patients too good to treat with intravenous thrombolysis[J]. Stroke,2016,47(12):2986-2992.
[10]Kim JT,Park MS,Choi KH,et al. Clinical outcomes of posterior versus anterior circulation infarction with low National Institutes of Health stroke scale scores[J]. Stroke,2017,48(1):55-62.
[11]Emberson J,Lees KR,Lyden P,et al. Effect of treatment delay,age,and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke:a meta-analysis of individual patient data from randomised trials[J]. Lancet,2014,384(9958):1929-1935.
[12]Greisenegger S,Seyfang L,Kiechl S,et al. Thrombolysis in patients with mild stroke:results from the Austrian Stroke Unit Registry[J].Stroke,2014,45(3):765-769.
[13]Laurencin C,Philippeau F,Blanc-Lasserre K,et al. Thrombolysis for acute minor stroke:outcome and barriers to management. Results from the RESUVAL stroke network[J]. Cerebrovasc Dis,2015,40(1/2):3-9.
[14]Khatri P,Kleindorfer DO,Yeatts SD,et al. Strokes with minor symptoms:an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials[J]. Stroke,2010,41(11):2581-2586.
[15]Spokoyny I,Raman R,Ernstrom K,et al. Defining mild stroke:outcomes analysis of treated and untreated mild stroke patients[J]. J Stroke Cerebrovasc Dis,2015,24(6):1276-1281.
[16]Romano JG,Smith EE,Liang L,et al. Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis:a retrospective analysis of the Get With the Guidelines-Stroke registry[J]. JAMA Neurol,2015,72(4):423-431.
[17]中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组.中国急性缺血性脑卒中诊治指南2014[J].中华神经科杂志,2015,48(4):246-257.
[18]Hacke W,Kaste M,Bluhmki E,et al. Thrombolysis with alteplase 3to 4. 5 hours after acute ischemic stroke[J]. N Engl J Med,2008,359(13):1317-1329.
[19]Khatri P,Tayama D,Cohen G,et al. Effect of intravenous recombinant tissue-type plasminogen activator in patients with mild stroke in the third international stroke trial-3:post hoc analysis[J]. Stroke,2015,46(8):2325-2327.
[20]Yang J,Yu F,Liu H,et al. A Retrospective study of thrombolysis with 0. 6 mg/kg recombinant tissue plasminogen activator(rt-PA)in mild stroke[J]. Sci Rep,2016,6(8):31344.
[21]Ng FC,Coote S,Frost T,et al. Utility of computed tomographic perfusion in thrombolysis for minor stroke[J]. Stroke,2016,47(7):1914-1916.
[22]Seners P,Turc G,Tisserand M,et al. Unexplained early neurological deterioration after intravenous thrombolysis:incidence,predictors,and associated factors[J]. Stroke,2014,45(7):2004-2009.
[23]Smith EE,Abdullah AR,Petkovska I,et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke[J]. Stroke,2005,36(11):2497-2499.
[24]Rajajee V,Kidwell C,Starkman S,et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke[J]. Neurology,2006,67(6):980-984.
[25]Willey JZ,Stillman J,Rivolta JA,et al. Too good to treat? Outcomes in patients not receiving thrombolysis due to mild deficits or rapidly improving symptoms[J]. Int J Stroke,2012,7(3):202-206.
[26]Strbian D,Piironen K,Meretoja A,et al. Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms[J].Int J Stroke,2013,8(5):293-299.
[27]Khrmann M,Nowe T,Huttner HB,et al. Safety and outcome after thrombolysis in stroke patients with mild symptoms[J]. Cerebrovasc Dis,2009,27(2):160-166.
[28]Hao Z,Liu M,Wang D,et al. Etiologic subtype predicts outcome in mild stroke:prospective data from a hospital stroke registry[J]. BMC Neurol,2013,13(10):154.