Tang Xiuying, Li Runjun, Jing Quanmin, Wang Qingsheng, Liu Peng, Zhang Peidong, Liu Yingfeng
*Department of Cardiology, Zhujiang Hospital of Southern Medical University, GuangZhou, China; Departments of †Cardiology; and ‡Emergency Medicine, The First Hospital of QinHuangDao, QinHuangDao, China; and §Department of Cardiology, General Hospital of Shenyang Military Area Command, Shenyang, China.
J Cardiovasc Pharmacol. 2016 Aug;68(2):115-20. doi: 10.1097/FJC.0000000000000390.
Ticagrelor improves the clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). However, few studies have directly compared the efficacy and safety of ticagrelor against clopidogrel, an oral, thienopyridine-class antiplatelet drug. This study compared the efficacy and safety of ticagrelor and clopidogrel in patients with STEMI undergoing PPCI.
We enrolled 400 patients with STEMI undergoing PPCI at the Zhujiang Hospital of Southern Medical University and the First Hospital of Qinhuangdao, China, between January 01, 2013 and April 30, 2015. All patients received 300 mg of aspirin and were randomized to receive one of the following treatments: (1) a loading dose of clopidogrel (600 mg) before PPCI followed by clopidogrel (75 mg once daily for 1 year) post PPCI or (2) a loading dose of ticagrelor (180 mg) before PPCI followed by ticagrelor (90 mg twice daily for 1 year) post PPCI. Some patients were treated by intracoronary bolus of a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor [tirofiban (10 μg/kg) plus maintenance infusion (0.15 μg·kg·min) for 24-36 hours] in accordance with specified guidelines. The primary end points evaluated were major adverse cardiovascular and cerebrovascular event (MACCE) [defined as a composite of overall death, myocardial infarction (MI), unplanned revascularization, or stroke], stent thrombosis, and the composite end point of CV death, nonfatal MI, and stroke. The supplemental use of GPIIb/IIIa inhibitors in the clopidogrel and ticagrelor groups was monitored as another study end point, although the secondary safety end point evaluated was the incidence of bleeding events.
Compared with the clopidogrel-treated group, ticagrelor treatment significantly reduced the incidence of MACCE [5 vs. 14; odds ratio (OR), 0.341; 95% confidence interval (CI), 0.120-0.964; P = 0.034] and the composite end points of cardiovascular death, nonfatal MI, and stroke (4 vs. 13; OR, 0.294; 95% CI, 0.094-0.916; P = 0.026). Fewer patients in the ticagrelor group received GPIIb/IIIa inhibitors after PPCI compared with those in the clopidogrel group (10 vs. 21; OR, 0.449; 95% CI, 0.206-0.979; P = 0.040). However, there were no significant differences between the groups in the incidences of all-cause mortality, nonfatal MI, unplanned revascularization, stroke, stent thrombosis (P = 0.522, P = 0.246, P = 0.246, P = 0.217, P = 0.246, respectively), or bleeding events (10 vs. 7; OR, 1.451; 95% CI, 0.541-3.891; P = 0.457).
Among patients with STEMI undergoing PPCI, ticagrelor reduces the incidence of MACCE and the composite end point of cardiovascular death, nonfatal MI, and stroke compared with clopidogrel. Ticagrelor also reduces the need for GPIIb/IIIa inhibitors. However, no significant difference was observed in the risk of bleeding between the 2 groups.
替格瑞洛可改善接受直接经皮冠状动脉介入治疗(PPCI)的ST段抬高型心肌梗死(STEMI)患者的临床结局。然而,很少有研究直接比较替格瑞洛与口服噻吩并吡啶类抗血小板药物氯吡格雷的疗效和安全性。本研究比较了替格瑞洛和氯吡格雷在接受PPCI的STEMI患者中的疗效和安全性。
2013年1月1日至2015年4月30日期间,我们纳入了在中国南方医科大学珠江医院和秦皇岛市第一医院接受PPCI的400例STEMI患者。所有患者均服用300mg阿司匹林,并随机接受以下治疗之一:(1)PPCI前给予氯吡格雷负荷剂量(600mg),PPCI后给予氯吡格雷(75mg每日一次,共1年);或(2)PPCI前给予替格瑞洛负荷剂量(180mg),PPCI后给予替格瑞洛(90mg每日两次,共1年)。部分患者根据特定指南通过冠状动脉内推注糖蛋白IIb/IIIa(GPIIb/IIIa)抑制剂[替罗非班(10μg/kg)加维持输注(0.15μg·kg·min),持续24 - 36小时]进行治疗。评估的主要终点为主要不良心血管和脑血管事件(MACCE)[定义为全因死亡、心肌梗死(MI)、非计划血管重建或卒中的综合指标]、支架血栓形成以及心血管死亡、非致命性MI和卒中的复合终点。氯吡格雷组和替格瑞洛组中GPIIb/IIIa抑制剂的补充使用情况作为另一项研究终点进行监测,尽管评估的次要安全终点是出血事件的发生率。
与氯吡格雷治疗组相比,替格瑞洛治疗显著降低了MACCE的发生率[5例 vs. 14例;比值比(OR),0.341;95%置信区间(CI),0.120 - 0.964;P = 0.034]以及心血管死亡、非致命性MI和卒中的复合终点(4例 vs. 13例;OR,0.294;95%CI,0.094 - 0.916;P = 0.026)。与氯吡格雷组相比,替格瑞洛组PPCI后接受GPIIb/IIIa抑制剂的患者更少(10例 vs. 21例;OR,0.449;95%CI,0.206 - 0.979;P = 0.040)。然而,两组在全因死亡率、非致命性MI、非计划血管重建、卒中、支架血栓形成的发生率(分别为P = 0.522、P = 0.246、P = 0.246、P = 0.217、P = 0.246)或出血事件方面(10例 vs. 7例;OR,1.451;95%CI,0.541 - 3.891;P = 0.457)无显著差异。
在接受PPCI的STEMI患者中,与氯吡格雷相比,替格瑞洛降低了MACCE的发生率以及心血管死亡、非致命性MI和卒中的复合终点。替格瑞洛还减少了对GPIIb/IIIa抑制剂的需求。然而,两组在出血风险方面未观察到显著差异。