Research Institute, Heart Hospital, São Paulo, Brazil.
Instituto do Coração, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
JAMA Cardiol. 2018 May 1;3(5):391-399. doi: 10.1001/jamacardio.2018.0612.
The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain.
To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy.
DESIGN, SETTING AND PARTICIPANTS: We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%.
Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel.
The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days.
The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57).
In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.
clinicaltrials.gov Identifier: NCT02298088.
在接受溶栓治疗的 ST 段抬高型心肌梗死患者中，替格瑞洛的出血安全性仍不确定。
评估替格瑞洛与氯吡格雷相比在接受溶栓治疗的 ST 段抬高型心肌梗死患者中的短期安全性。
设计、地点和参与者：我们进行了一项多中心、随机、开放标签、盲终点评估试验，纳入了来自 10 个国家的 152 个地点的 3799 例（年龄<75 岁）接受溶栓治疗的 ST 段抬高型心肌梗死患者。出血非劣效性的预设上限为 1.0%。
患者被随机分配至替格瑞洛（180mg 负荷剂量，随后 90mg 每日两次）或氯吡格雷（300-600mg 负荷剂量，随后 75mg 每日一次）。患者在溶栓后中位数 11.4 小时被随机分组，90%的患者预先接受氯吡格雷治疗。
主要结局为 30 天内的心肌梗死溶栓治疗（TIMI）大出血。
平均（标准差）年龄为 58.0（9.5）岁，3799 例患者中 2928 例（77.1%）为男性，3799 例患者中 2177 例（57.3%）为白人。30 天时，替格瑞洛组 1913 例患者中有 14 例（0.73%）发生 TIMI 大出血，氯吡格雷组 1886 例患者中有 13 例（0.69%）发生 TIMI 大出血（绝对差值，0.04%；95%CI，-0.49%至 0.58%；P<0.001 用于非劣效性）。根据血小板抑制和患者结局标准以及出血学术研究联合会 3 至 5 型出血定义，替格瑞洛组 23 例（1.20%）和氯吡格雷组 26 例（1.38%）发生大出血（绝对差值，-0.18%；95%CI，-0.89%至 0.54%；P=0.001 用于非劣效性）。替格瑞洛组和氯吡格雷组分别有 0.16%（0.11%；P=0.67）和 0.42%（0.37%；P=0.82）的患者发生致命性和颅内出血。替格瑞洛组比氯吡格雷组更常见轻微和微小出血。替格瑞洛组 76 例（4.0%）和氯吡格雷组 82 例（4.3%）患者发生血管原因死亡、心肌梗死或卒中的复合终点（风险比，0.91；95%CI，0.67-1.25；P=0.57）。
在年龄<75 岁的 ST 段抬高型心肌梗死患者中，溶栓治疗后延迟给予替格瑞洛与氯吡格雷相比，30 天时 TIMI 大出血的非劣效性。
clinicaltrials.gov 标识符：NCT02298088。
