Tenecteplase Thrombolysis for Acute Ischemic Stroke.
Tenecteplase Thrombolysis for Acute Ischemic Stroke.
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DOI：
10.1161/strokeaha.120.029749
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发表时间：
2020-11
期刊：
影响因子：
8.3
通讯作者：
Milling TJ Jr
中科院分区：
文献类型：
--
作者：
Warach SJ;Dula AN;Milling TJ Jr
替奈普酶是一种纤溶药物，与标准卒中溶栓药物阿替普酶相比，具有更高的纤维蛋白特异性和更长的半衰期，便于单次推注给药。0.5 mg/kg替奈普酶已获得监管机构批准用于治疗ST段抬高型心肌梗死，其30天死亡率相当，全身性损害较少。在过去15年中，替奈普酶作为缺血性卒中的溶栓药物进行了研究，目前正在进行多项III期试验。基于系统性文献检索，我们提供了已发表的替奈普酶卒中临床试验的定性综合，这些试验（1）与阿替普酶进行了随机比较，（2）比较了不同剂量的替奈普酶，或（3）提供了独特的定量荟萃分析。4项II期和1项III期研究对阿替普酶进行了随机比较。这些和其他II期研究比较了不同替奈普酶剂量和对再通、再灌注和实质性神经功能改善的早期结局以及症状性颅内出血和3个月残疾（改良兰金评分）的影响。尽管没有一项试验前瞻性证明替奈普酶在临床结局方面的优效性或非劣效性，但这些试验的荟萃分析（1585例随机化患者）指出，替奈普酶在大血管闭塞再通方面具有优效性，在3个月无残疾结局方面具有非劣效性，且不增加症状性颅内出血或死亡率。已对0.25 mg/kg和0.4 mg/kg的剂量进行了试验，但结果未表明较高剂量的优势。目前的卒中临床实践指南包括静脉注射替奈普酶作为二级选择，根据一项II期试验，推荐0.25 mg/kg剂量用于大血管闭塞，该试验证明了相对于阿替普酶的上级再通和3个月结局改善。正在进行的随机化III期试验可能更好地定义替奈普酶和阿替普酶用于卒中溶栓的比较风险和获益，并回答在大于4.5小时的时间窗内、唤醒卒中中以及与血管内血栓切除术联合使用时替奈普酶疗效的问题。
Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the last 15 years, tenecteplase is currently being studies in several Phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four Phase 2 and one Phase 3 study performed randomized comparisons with alteplase. These and other Phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurologic improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin score. Although no single trial prospectively demonstrated superiority or non-inferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and non-inferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 mg/kg and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a Phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized Phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the greater than 4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.