Mehta Shamir R, Boden William E, Eikelboom John W, Flather Marcus, Steg P Gabriel, Avezum Alvaro, Afzal Rizwan, Piegas Leopoldo S, Faxon David P, Widimsky Petr, Budaj Andrzej, Chrolavicius Susan, Rupprecht Hans-Jurgen, Jolly Sanjit, Granger Christopher B, Fox Keith A A, Bassand Jean-Pierre, Yusuf Salim
McMaster University, Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.
Circulation. 2008 Nov 11;118(20):2038-46. doi: 10.1161/CIRCULATIONAHA.108.789479. Epub 2008 Oct 27.
The Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials evaluated fondaparinux, a synthetic factor Xa inhibitor, in patients with non-ST- and ST-segment elevation acute coronary syndromes, respectively. Combined results for these 2 trials on major efficacy and safety outcomes and data on the effects of fondaparinux in relation to interventional management strategy have not been previously reported.
We performed an individual patient-level combined analysis of 26 512 patients from the OASIS 5 and 6 trials who were randomized in a double-blind fashion to fondaparinux 2.5 mg daily or a heparin-based strategy (dose-adjusted unfractionated heparin or enoxaparin). Results were stratified according to whether an early invasive, a delayed invasive, or an initial conservative management strategy was performed. Fondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P=0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P=0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P<0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P<0.0001). In 19 085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P=0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P<0.001).
Compared with a heparin-based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
第五和第六次缺血综合征策略评估组织（OASIS 5和6）试验分别评估了合成Xa因子抑制剂磺达肝癸钠在非ST段抬高型和ST段抬高型急性冠状动脉综合征患者中的应用。此前尚未报道这两项试验关于主要疗效和安全性结局的联合结果，以及磺达肝癸钠在介入管理策略方面的影响数据。
我们对OASIS 5和6试验中的26512例患者进行了个体患者水平的联合分析，这些患者以双盲方式随机分为每日2.5mg磺达肝癸钠组或基于肝素的策略组（剂量调整的普通肝素或依诺肝素）。结果根据是否采用早期侵入性、延迟侵入性或初始保守管理策略进行分层。在降低死亡、心肌梗死或卒中的复合终点方面，磺达肝癸钠优于肝素（8.0%对7.2%；风险比[HR]，0.91；P=0.03），在降低单独死亡方面也优于肝素（4.3%对3.8%；HR，0.89；P=0.05）。磺达肝癸钠使大出血减少41%（3.4%对2.1%；HR，0.59；P<0.00001），且净临床结局比肝素更有利（11.1%对9.3%；HR，0.83；P<0.0001）。在19085例接受侵入性策略治疗的患者中，磺达肝癸钠抑制缺血事件的程度与肝素相似，且大出血减少超过一半，导致净临床结局更优（10.8%对9.4%；HR，0.87；P=0.008）。在接受保守策略治疗的患者中也观察到了类似的益处（HR，0.74；95%置信区间，0.64至0.85；P<0.001）。
与基于肝素的策略相比，磺达肝癸钠在整个急性冠状动脉综合征范围内降低了死亡率、缺血事件和大出血，并且在接受侵入性或保守管理策略的患者中与更有利的净临床结局相关。
