Abstract：
BACKGROUND: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear.
METHODS: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset.
RESULTS: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).
CONCLUSIONS: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).
METHODS: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset.
RESULTS: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).
CONCLUSIONS: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).
摘要：
背景：阿替普酶是用于早期再灌注治疗的标准药物，但需要其他溶栓药物.与阿替普酶相比，瑞替普酶在急性缺血性卒中患者中的疗效和安全性尚不清楚。
方法：我们以1:1的比例将症状发作后4.5小时内的缺血性卒中患者随机分配给静脉注射瑞替普酶（推注18毫克，30分钟后第二次推注18毫克）或静脉注射阿替普酶（每公斤体重0.9毫克；最大剂量，90毫克）。主要疗效结果是出色的功能结果，定义为修改后的Rankin量表上的0或1分(范围，0[无神经缺陷，没有症状,或完全恢复]至6[死亡])在90天。主要安全性结果是症状发作后36小时内有症状的颅内出血。
结果：总共707名患者被分配接受瑞替普酶，705人被分配接受阿替普酶治疗。瑞替普酶组79.5%的患者和阿替普酶组70.4%的患者出现了极好的功能结果(风险比，1.13；95%置信区间[CI]，1.05至1.21；非劣性P<0.001，优越性P=0.002）。瑞替普酶组700例患者中有17例（2.4％），阿替普酶组699例患者中有14例（2.0％）（风险比，1.21；95%CI，0.54至2.75）。瑞替普酶在90天颅内出血的发生率高于阿替普酶（7.7％vs.4.9%；风险比，1.59；95%CI，1.00至2.51），不良事件的发生率(91.6%vs.82.4%；风险比，1.11；95%CI，1.03至1.20）。
结论：在症状发作后4.5小时内的缺血性卒中患者中，瑞替普酶比阿替普酶更可能导致出色的功能结果。(由华润昂德生物科技制药等资助；RAISEClinicalTrials.gov编号，NCT05295173。).
方法：我们以1:1的比例将症状发作后4.5小时内的缺血性卒中患者随机分配给静脉注射瑞替普酶（推注18毫克，30分钟后第二次推注18毫克）或静脉注射阿替普酶（每公斤体重0.9毫克；最大剂量，90毫克）。主要疗效结果是出色的功能结果，定义为修改后的Rankin量表上的0或1分(范围，0[无神经缺陷，没有症状,或完全恢复]至6[死亡])在90天。主要安全性结果是症状发作后36小时内有症状的颅内出血。
结果：总共707名患者被分配接受瑞替普酶，705人被分配接受阿替普酶治疗。瑞替普酶组79.5%的患者和阿替普酶组70.4%的患者出现了极好的功能结果(风险比，1.13；95%置信区间[CI]，1.05至1.21；非劣性P<0.001，优越性P=0.002）。瑞替普酶组700例患者中有17例（2.4％），阿替普酶组699例患者中有14例（2.0％）（风险比，1.21；95%CI，0.54至2.75）。瑞替普酶在90天颅内出血的发生率高于阿替普酶（7.7％vs.4.9%；风险比，1.59；95%CI，1.00至2.51），不良事件的发生率(91.6%vs.82.4%；风险比，1.11；95%CI，1.03至1.20）。
结论：在症状发作后4.5小时内的缺血性卒中患者中，瑞替普酶比阿替普酶更可能导致出色的功能结果。(由华润昂德生物科技制药等资助；RAISEClinicalTrials.gov编号，NCT05295173。).
