TIMI Study Group, Brigham and Women's Hospital, Boston, MA 02115, USA.
Lancet. 2010 Jan 23;375(9711):283-93. doi: 10.1016/S0140-6736(09)62191-7. Epub 2010 Jan 13.
Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients.
At randomisation, an invasive strategy was planned for 13 408 (72.0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872.
6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9.0%] vs 668 [10.7%], hazard ratio 0.84, 95% CI 0.75-0.94; p=0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11.6%] vs 689 [11.5%], 0.99 [0.89-1.10]; p=0.8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3.2%] vs 185 [2.9%], 0.91 [0.74-1.12]; p=0.3785).
Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.
氯吡格雷的血小板抑制作用存在变异性且不可逆转，这导致人们对其在急性冠状动脉综合征患者中的最佳剂量和给药时间存在争议。我们比较了替格瑞洛，一种更强效的可逆 P2Y12 抑制剂与氯吡格雷在这类患者中的作用。
在随机分组时，计划对 18624 例因急性冠状动脉综合征（伴或不伴 ST 段抬高）住院的患者中的 13408 例（72.0%）进行有创策略。在一项双盲、双模拟研究中，患者以 1:1 的比例随机分配接受替格瑞洛和安慰剂（负荷剂量 180mg，随后每天两次 90mg）或氯吡格雷和安慰剂（负荷剂量 300-600mg 或维持剂量后每天 75mg）治疗 6-12 个月。所有患者均给予阿司匹林。主要复合终点为心血管死亡、心肌梗死或卒中。分析采用意向治疗。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00391872。
6732 例患者被分配至替格瑞洛组，6676 例患者被分配至氯吡格雷组。替格瑞洛组患者的主要复合终点事件发生率低于氯吡格雷组（360 天的发生率分别为 569[9.0%]和 668[10.7%]，风险比 0.84，95%CI 0.75-0.94；p=0.0025）。氯吡格雷组与替格瑞洛组的总大出血发生率（分别为 691[11.6%]和 689[11.5%]，0.99[0.89-1.10]；p=0.8803）或按全球采用策略开通闭塞冠状动脉（GUSTO）定义的严重出血发生率（分别为 198[3.2%]和 185[2.9%]，0.91[0.74-1.12]；p=0.3785）无差异。
对于计划早期采用有创策略的急性冠状动脉综合征患者，替格瑞洛似乎优于氯吡格雷。
