Wiviott Stephen D, Braunwald Eugene, McCabe Carolyn H, Montalescot Gilles, Ruzyllo Witold, Gottlieb Shmuel, Neumann Franz-Joseph, Ardissino Diego, De Servi Stefano, Murphy Sabina A, Riesmeyer Jeffrey, Weerakkody Govinda, Gibson C Michael, Antman Elliott M
Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4.
Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention.
To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel (a 60-mg loading dose and a 10-mg daily maintenance dose) or clopidogrel (a 300-mg loading dose and a 75-mg daily maintenance dose), for 6 to 15 months. The primary efficacy end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding.
The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (hazard ratio for prasugrel vs. clopidogrel, 0.81; 95% confidence interval [CI], 0.73 to 0.90; P<0.001). We also found significant reductions in the prasugrel group in the rates of myocardial infarction (9.7% for clopidogrel vs. 7.4% for prasugrel; P<0.001), urgent target-vessel revascularization (3.7% vs. 2.5%; P<0.001), and stent thrombosis (2.4% vs. 1.1%; P<0.001). Major bleeding was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients receiving clopidogrel (hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P=0.03). Also greater in the prasugrel group was the rate of life-threatening bleeding (1.4% vs. 0.9%; P=0.01), including nonfatal bleeding (1.1% vs. 0.9%; hazard ratio, 1.25; P=0.23) and fatal bleeding (0.4% vs. 0.1%; P=0.002).
In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups. (ClinicalTrials.gov number, NCT00097591 [ClinicalTrials.gov].)
阿司匹林与噻吩并吡啶类药物联合进行双重抗血小板治疗是预防急性冠脉综合征和经皮冠状动脉介入治疗血栓形成并发症的治疗基石。
为比较新型噻吩并吡啶类药物普拉格雷与氯吡格雷的疗效，我们将13608例中高危急性冠脉综合征且计划接受经皮冠状动脉介入治疗的患者随机分组，分别给予普拉格雷（负荷剂量60mg，每日维持剂量10mg）或氯吡格雷（负荷剂量300mg，每日维持剂量75mg），治疗6至15个月。主要疗效终点为心血管原因导致的死亡、非致死性心肌梗死或非致死性卒中。关键安全性终点为大出血。
接受氯吡格雷治疗的患者中主要疗效终点发生率为12.1%，接受普拉格雷治疗的患者为9.9%（普拉格雷与氯吡格雷相比的风险比为0.81；95%置信区间[CI]为0.73至0.90；P<0.001）。我们还发现普拉格雷组中心肌梗死发生率（氯吡格雷组为9.7%，普拉格雷组为7.4%；P<0.001）、紧急靶血管血运重建率（3.7%对2.5%；P<0.001）和支架内血栓形成率（2.4%对1.1%；P<0.001）均显著降低。接受普拉格雷治疗的患者中有2.4%发生大出血，接受氯吡格雷治疗的患者中有1.8%发生大出血（风险比为1.32；95%CI为1.03至1.68；P=0.03）。普拉格雷组危及生命的出血发生率也更高（1.4%对0.9%；P=0.01），包括非致死性出血（1.1%对0.9%；风险比为1.25；P=0.23）和致死性出血（0.4%对0.1%；P=0.002）。
在计划接受经皮冠状动脉介入治疗的急性冠脉综合征患者中，普拉格雷治疗与缺血事件发生率显著降低相关，包括支架内血栓形成，但大出血风险增加，包括致死性出血。治疗组间总体死亡率无显著差异。（ClinicalTrials.gov编号，NCT00097591 [ClinicalTrials.gov]。）
