Cohen Marc, Mahaffey Kenneth W, Pieper Karen, Pollack Charles V, Antman Elliott M, Hoekstra James, Goodman Shaun G, Langer Anatoly, Col Jacques J, White Harvey D, Califf Robert M, Ferguson James J
HEART Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, New Jersey 07112, USA.
J Am Coll Cardiol. 2006 Oct 3;48(7):1346-54. doi: 10.1016/j.jacc.2006.05.058. Epub 2006 Sep 12.
The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial.
The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment.
Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days.
After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding.
Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.
本研究旨在比较在SYNERGY（依诺肝素、血管重建和糖蛋白IIb/IIIa抑制剂新策略的卓越疗效）试验中，随机分组前接受抗凝血酶预处理的效果以及依诺肝素与普通肝素（UFH）的总体疗效和安全性。
SYNERGY试验结果表明，依诺肝素与UFH相比，在结局方面具有非劣效性。随机治疗与随机分组前的治疗无关。
首先对4个随机分组前的亚组进行分析：未接受抗凝血酶治疗的患者以及接受依诺肝素或UFH或两者治疗的患者。然后，我们关注未接受预处理或接受预处理并随机分组至同一药物的患者亚组。在9978例患者中，2440例未接受随机分组前治疗，6138例在随机分组过程中接受了一致的治疗。主要终点是30天时死亡和非致命性心肌梗死（MI）的复合终点。
在对亚组间差异进行调整后，4个预处理组与死亡或MI之间的关联无显著差异（p = 0.171）。随机治疗对30天死亡或MI的影响倾向于随预处理而变化（调整后的交互检验p = 0.055）。接受依诺肝素一致治疗的患者死亡或MI显著少于随机分组至UFH的患者（调整后p = 0.041），且有出血增加的趋势。
随机分组前的抗凝血酶治疗可能会对研究药物效果的比较产生潜在影响。在对亚组间基线特征差异进行调整后，依诺肝素的一致治疗在降低死亡或非致命性MI方面可能优于UFH，但出血略有增加。
