利伐沙班用于近期急性冠状动脉综合征患者。
Rivaroxaban in patients with a recent acute coronary syndrome.
机构信息
Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
出版信息
N Engl J Med. 2012 Jan 5;366(1):9-19. doi: 10.1056/NEJMoa1112277. Epub 2011 Nov 13.
BACKGROUND
Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.
METHODS
In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.
RESULTS
Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).
CONCLUSIONS
In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).
背景
急性冠状动脉综合征源于伴有血栓形成的冠状动脉粥样硬化。由于因子 Xa 在血栓形成中起核心作用，因此用小剂量利伐沙班抑制因子 Xa 可能会改善近期急性冠状动脉综合征患者的心血管结局。
方法
在这项双盲、安慰剂对照试验中，我们将 15526 例近期发生急性冠状动脉综合征的患者随机分为每日两次接受 2.5mg 或 5mg 利伐沙班或安慰剂治疗，平均随访 13 个月，最长可达 31 个月。主要疗效终点是心血管原因死亡、心肌梗死或卒中的复合终点。
结果
与安慰剂相比，利伐沙班显著降低了主要疗效终点，其发生率分别为 8.9%和 10.7%（利伐沙班组的危险比为 0.84；95%置信区间[CI]为 0.74 至 0.96；P=0.008），每日两次 2.5mg 剂量（9.1% vs. 10.7%，P=0.02）和每日两次 5mg 剂量（8.8% vs. 10.7%，P=0.03）均有显著改善。每日两次 2.5mg 剂量的利伐沙班降低了心血管原因死亡（2.7% vs. 4.1%，P=0.002）和任何原因导致的死亡（2.9% vs. 4.5%，P=0.002）的发生率，而每日两次 5mg 剂量未观察到这种生存获益。与安慰剂相比，利伐沙班增加了不与冠状动脉旁路移植术相关的主要出血（2.1% vs. 0.6%，P<0.001）和颅内出血（0.6% vs. 0.2%，P=0.009）的发生率，但致命性出血无显著增加（0.3% vs. 0.2%，P=0.66）或其他不良事件。每日两次 2.5mg 剂量导致的致命性出血事件少于每日两次 5mg 剂量（0.1% vs. 0.4%，P=0.04）。
结论
在近期发生急性冠状动脉综合征的患者中，利伐沙班降低了心血管原因死亡、心肌梗死或卒中的复合终点风险。利伐沙班增加了大出血和颅内出血的风险，但没有增加致命性出血的风险。（由 Johnson & Johnson 和 Bayer Healthcare 资助；ATLAS ACS 2-TIMI 51 ClinicalTrials.gov 编号，NCT00809965。）
Zotero 插件