Zong Lixia, Wang Liyuan, Jin Aoming, Ma Yujie, Feng Xueyan, Wang Hao, Wang Ziran, Dai Hongguo, Che Fengyuan, Wang Lihua, Zhou Li, Xiong Yunyun, Wang Yongjun
Vascular Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Vascular Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
J Stroke Cerebrovasc Dis. 2025 Oct;34(10):108409. doi: 10.1016/j.jstrokecerebrovasdis.2025.108409. Epub 2025 Jul 29.
Concerns regarding bleeding risks have limited the use of intravenous thrombolysis in acute ischemic stroke (AIS) patients with renal dysfunction (RD). This study investigated the impact of RD on the efficacy and safety of Tenecteplase (TNK) thrombolysis in AIS patients with large vessel occlusions (LVO) beyond the 4.5 h window.
This post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III (TRACE-III) Trial included 510 patients with LVO (4.5-24 h from onset) randomized to TNK (0.25 mg/kg) or standard medical treatment (SMT). Renal function was categorized as normal (eGFR ≥90 mL/min/1.73 m²), mild (eGFR 60-89), or moderate-to-severe RD (eGFR <60). Primary efficacy outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] 0-1). Safety outcomes included symptomatic intracerebral hemorrhage (sICH), mortality and moderate or severe bleeding within 90 days. Multivariable regression and linear models were used to assess treatment effects across eGFR strata.
In normal renal function patients (n = 410), TNK showed numerically higher excellent outcomes (32.3 % vs. 24.2 %, RR=1.28, 95 % CI 0.94∼1.75) and improved secondary outcomes (neurological improvement, as defined by NIHSS score reduction at 24 h/72 h/7 d and reperfusion rates), albeit with increased sICH (3.2 % vs. 1.1 %, p = 0.05). For mild RD (n = 82), TNK demonstrated a non-significant trend toward better functional outcomes (40.6 % vs. 26.0 %, RR=1.52, 95 % CI 0.78∼2.96). In moderate-to-severe RD (n = 18), outcomes were inconclusive due to limited sample size.
TNK may benefit late-window LVO stroke patients with normal or mildly impaired renal function. The risk-benefit profile in moderate-to-severe RD remains uncertain, highlighting the need for larger prospective studies in this high-risk population.
对出血风险的担忧限制了静脉溶栓在肾功能不全（RD）的急性缺血性卒中（AIS）患者中的应用。本研究调查了RD对超过4.5小时时间窗的AIS大血管闭塞（LVO）患者替奈普酶（TNK）溶栓疗效和安全性的影响。
这项对急性缺血性脑血管事件-III（TRACE-III）试验中替奈普酶再灌注治疗的事后分析纳入了510例LVO患者（发病后4.5 - 24小时），随机分为TNK组（0.25mg/kg）或标准药物治疗（SMT）组。肾功能分为正常（估算肾小球滤过率[eGFR]≥90mL/min/1.73m²）、轻度（eGFR 60 - 89）或中重度RD（eGFR <60）。主要疗效结局为90天良好功能结局（改良Rankin量表[mRS] 0 - 1）。安全性结局包括症状性脑出血（sICH）、死亡率以及90天内的中度或重度出血。采用多变量回归和线性模型评估不同eGFR分层的治疗效果。
在肾功能正常的患者（n = 410）中，TNK在数值上显示出更高的良好结局（32.3%对24.2%，RR = 1.28，95%CI 0.94∼1.75），并且次要结局有所改善（神经功能改善，定义为24小时/72小时/7天时美国国立卫生研究院卒中量表[NIHSS]评分降低以及再灌注率），尽管sICH有所增加（3.2%对1.1%，p = 0.05）。对于轻度RD患者（n = 82），TNK在功能结局改善方面显示出无显著差异的趋势（40.6%对26.0%，RR = 1.52，95%CI 0.78∼2.96）。在中重度RD患者（n = 18）中，由于样本量有限，结局尚无定论。
TNK可能使肾功能正常或轻度受损的晚期时间窗LVO卒中患者获益。中重度RD患者的风险效益情况仍不确定，这凸显了在这一高风险人群中开展更大规模前瞻性研究的必要性。
