Institut de Cardiologie, Centre Hospitalier Universitaire Pitié–Salpêtrière (ACTION group, Assistance Publique–Hôpitaux de Paris [AP-HP], Université Paris 6), Paris, France.
N Engl J Med. 2013 Sep 12;369(11):999-1010. doi: 10.1056/NEJMoa1308075. Epub 2013 Sep 1.
Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated.
We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group.
The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups.
Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).
尽管 P2Y12 拮抗剂在非 ST 段抬高（NSTE）急性冠状动脉综合征患者中有效，但给药时间（在冠状动脉造影之前或之后）的效果尚不清楚。我们评估了在诊断时给予 P2Y12 拮抗剂普拉格雷与如果需要经皮冠状动脉介入治疗（PCI）则在冠状动脉造影后给予的效果。
我们纳入了 4033 名计划在随机分组后 2 至 48 小时内行冠状动脉造影的 NSTE 急性冠状动脉综合征且肌钙蛋白水平阳性的患者。患者被随机分配接受普拉格雷（30 毫克负荷剂量）治疗（预处理组）或安慰剂（对照组）。当需要 PCI 时，在预处理组中于 PCI 时给予额外的 30 毫克普拉格雷，在对照组中给予 60 毫克普拉格雷。
主要疗效终点（心血管原因死亡、心肌梗死、卒中和紧急血运重建或糖蛋白 IIb/IIIa 抑制剂挽救治疗（糖蛋白 IIb/IIIa 解救）的复合终点）在两组之间无显著差异（预处理组的危险比为 1.02；95%置信区间[CI]，0.84 至 1.25；P=0.81）。7 天内所有 TIMI 主要出血事件（无论是否与冠状动脉旁路移植术[CABG]相关）的关键安全性终点的发生率在预处理组中增加（危险比，1.90；95%CI，1.19 至 3.02；P=0.006）。TIMI 主要出血和无 CABG 相关的危及生命的出血发生率分别增加了 3 倍和 6 倍。预处理并未降低接受 PCI（71%的患者）的患者主要结局的发生率，但增加了 7 天的 TIMI 主要出血发生率。所有结果在 30 天和预先指定的亚组中均得到证实。
在计划行导管插入术的 NSTE 急性冠状动脉综合征患者中，普拉格雷预处理并未降低 30 天内主要缺血事件的发生率，但增加了大出血并发症的发生率。（由 Daiichi Sankyo 和 Eli Lilly 资助；ACCOAST ClinicalTrials.gov 编号，NCT01015287。）
