替奈普酶与阿替普酶治疗串联病变卒中患者的安全性和有效性：EXTEND-IA TNK 试验的事后分析。
Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials.
机构信息
From the Department of Medicine and Neurology (V.Y., L.C., N.Y., B.Y., G.S., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville; Melbourne Medical School (L.C., V.T.), University of Melbourne, Heidelberg; Department of Radiology (P.J.M., B.C.V.C.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurology (T.J.K., B.Y., P.M.D.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Florey Institute of Neuroscience and Mental Health (V.T.), University of Melbourne, Parkville, Australia; Department of Neurology (T. Wu), Christchurch Hospital, New Zealand; Department of Neurology (D.S.), Princess Alexandra Hospital, Brisbane; Department of Neurology (P.B.), Gold Coast University Hospital, Southport; Department of Neurosciences (H.M.D., P.M.C.C.), Eastern Health and Eastern Health Clinical School, Monash University, Clayton; Royal North Shore Hospital (A.M.), New South Wales; Department of Medicine and Neurology (T. Wijeratne), Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans; Department of Neurology (C.G.-E.), John Hunter Hospital, Newcastle, New South Wales; Department of Neurology (G.C.), Alfred Hospital, Melbourne; Department of Neuroscience (G.C.), Central Clinical School, Monash University, Melbourne; NeuroInterventional Radiology Unit (R.V.C.), Monash Health, Monash University; and Department of Neurology (D.J.C., M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia.
出版信息
Neurology. 2023 May 2;100(18):e1900-e1911. doi: 10.1212/WNL.0000000000207138. Epub 2023 Mar 6.
BACKGROUND AND OBJECTIVES
The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs.
METHODS
We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK.
RESULTS
Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed.
DISCUSSION
Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.
背景与目的
替奈普酶（TNK）在串联病变（TL）卒中患者中的安全性和疗效尚不清楚。我们对 TNK 和阿替普酶在 TL 患者中的应用进行了比较分析。
方法
我们首先使用 EXTEND-IA TNK 试验的个体患者数据比较了 TL 患者中 TNK 和阿替普酶的治疗效果。我们使用有序逻辑和 Firth 回归模型评估了初始血管造影评估时的颅内再灌注和 90 天改良 Rankin 量表（mRS）。由于 EXTEND-IA TNK 试验中接受阿替普酶治疗的患者中死亡率和症状性颅内出血（sICH）这两个关键结局的数量较少，我们通过补充试验数据和系统评价中确定的研究的发生率的汇总估计值来生成这些结局的汇总估计值。然后，我们计算了未调整的风险差异，以比较接受阿替普酶治疗的患者的汇总估计值与接受 TNK 治疗的患者的试验中观察到的发生率。
结果
在 EXTEND-IA TNK 试验的 483 例患者中，有 71 例（15%）患有 TL。在 TL 患者中，颅内再灌注在 56 例 TNK 治疗患者中观察到 11 例（20%），在 15 例阿替普酶治疗患者中观察到 1 例（7%）（调整后的优势比 2.19；95%CI 0.28-17.29）。90 天 mRS 无显著差异（调整后的共同优势比 1.48；95%CI 0.44-5.00）。阿替普酶相关死亡率和 sICH 的 pooled study-level 比例分别为 0.14（95%CI 0.08-0.21）和 0.09（95%CI 0.04-0.16）。与 TNK 治疗患者的死亡率（0.09；95%CI 0.03-0.20）和 sICH 发生率（0.07；95%CI 0.02-0.17）相比，无显著差异。
讨论
TL 患者接受 TNK 和阿替普酶治疗的功能结局、死亡率和 sICH 无显著差异。
证据分类
这项研究提供了 III 级证据，表明在 TL 引起的急性卒中患者中，与阿替普酶相比，TNK 与颅内再灌注、功能结局、死亡率和 sICH 相似的发生率相关。然而，CI 不能排除临床上重要的差异。
试验注册信息
clinicaltrials.gov/ct2/show/NCT02388061；clinicaltrials.gov/ct2/show/NCT03340493。
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