替奈普酶在老年大血管闭塞患者中的安全性和有效性：EXTEND-IA TNK试验的汇总分析
Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials.
作者信息
Yogendrakumar Vignan, Churilov Leonid, Mitchell Peter J, Kleinig Timothy J, Yassi Nawaf, Thijs Vincent, Wu Teddy Y, Shah Darshan G, Ng Felix C, Dewey Helen M, Wijeratne Tissa, Yan Bernard, Desmond Patricia M, Parsons Mark W, Donnan Geoffrey Alan, Davis Stephen M, Campbell Bruce C V
机构信息
From the Department of Medicine and Neurology (V.Y., L.C., N.Y., F.C.N., B.Y., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville; Department of Medicine (L.C., V.T.), Austin Health, University of Melbourne, Heidelberg; Florey Institute of Neuroscience and Mental Health (L.C., V.T., B.C.V.C.) and Department of Radiology, Royal Melbourne Hospital (P.J.M., B.Y., P.M.D.), University of Melbourne, Parkville; Department of Neurology (T.J.K.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Neurology (T.Y.W.), Christchurch Hospital, New Zealand; Department of Neurology (D.G.S.), Princess Alexandra Hospital, Brisbane, Queensland; Eastern Health and Eastern Health Clinical School, Department of Neurosciences (H.M.D.), Monash University, Clayton, Victoria; Department of Medicine and Neurology (T.W.), Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans Victoria; and Department of Neurology (M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia.
出版信息
Neurology. 2022 Mar 22;98(12):e1292-e1301. doi: 10.1212/WNL.0000000000013302. Epub 2022 Jan 11.
BACKGROUND AND OBJECTIVES
Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion.
METHODS
We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models.
RESULTS
In patients >80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23-5.94) and reduced mortality (acOR 0.34, 95% CI 0.13-0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03-5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg.
DISCUSSION
TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients.
TRIAL REGISTRATION INFORMATION
NCT02388061, NCT03340493.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.
背景与目的
对80岁以上患者使用替奈普酶（TNK）的详细研究有限。我们研究的目的是评估0.25和0.40mg/kg剂量的TNK在80岁以上大血管闭塞患者中的安全性和有效性。
方法
我们对EXTEND-IA TNK随机对照试验（n = 502）进行了汇总分析。患者为因颅内颈内动脉、大脑中动脉或基底动脉闭塞导致缺血性卒中的成年人，症状发作后4.5小时内就诊。我们比较了0.25mg/kg TNK、0.40mg/kg TNK和0.90mg/kg阿替普酶的治疗效果，并按患者年龄（>80岁）进行分层。评估的结局包括90天改良Rankin量表（mRS）评分、全因死亡率和症状性颅内出血。通过混合效应比例优势和逻辑回归模型对治疗效果进行调整，以校正基线美国国立卫生研究院卒中量表评分、年龄以及从症状发作到穿刺的时间。
结果
在>80岁的患者（n = 137）中，与0.40mg/kg相比，0.25mg/kg TNK与90天mRS改善（中位数3对4，校正共同优势比（acOR）2.70，9%CI 1.23 - 5.94）和死亡率降低（acOR 0.34，95%CI 0.l3 - 0.91）相关联。与阿替普酶相比，0.25mg/kg TNK与90天mRS改善（中位数3对4，acOR 2.28，95%CI 1.03 - \5.05）相关联。在阿替普酶和0.40mg/kg TNK之间未检测到90天mRS或死亡率的差异。接受0.40mg/kg TNK治疗的患者中有4例出现症状性颅内出血，接受阿替普酶治疗的患者中有1例，接受0.25mg/kg TNK治疗的患者中无。在≤80岁的患者中，0.25mg/kg TNK、阿替普酶和0.40mg/kg TNK之间在90天mRS、死亡率或症状性颅内出血方面未观察到差异。
讨论
0.25mg/kg TNK与80岁以上患者90天mRS改善和死亡率降低相关联。在较年轻患者中未观察到各剂量之间的差异。
试验注册信息
NCT02388061，NCT03340493。
证据分级
本研究提供了II类证据，即对于80岁以上大血管闭塞性卒中患者，在血管内治疗前给予0.25mg/kg替奈普酶与90天时更好的功能结局相关联，且与0.40mg/kg替奈普酶或0.90mg/kg阿替普酶相比死亡率降低。
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