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纤维蛋白溶解剂与抗血栓药物联合使用的年龄、结局及治疗效果:来自新型溶栓药物安全性和有效性评估(ASSENT)-3及ASSENT-3 PLUS研究的结果

Age, outcomes, and treatment effects of fibrinolytic and antithrombotic combinations: findings from Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-3 and ASSENT-3 PLUS.

作者信息

Sinnaeve Peter R, Huang Yao, Bogaerts Kris, Vahanian Alec, Adgey Jennifer, Armstrong Paul W, Wallentin Lars, Van de Werf Frans J, Granger Christopher B

机构信息

Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium.

出版信息

Am Heart J. 2006 Oct;152(4):684.e1-9. doi: 10.1016/j.ahj.2006.07.005.

Abstract

BACKGROUND

Elderly patients with acute myocardial infarction are at particularly high risk for death and bleeding complications. The efficacy and safety of antithrombotic strategies in these patients remain unclear.

METHODS

To provide more insight into the risk and benefit of antithrombotic strategies in the elderly, we examined patients from the ASSENT-3 and ASSENT-3 PLUS trials with STEMI who were treated with tenecteplase (TNK) and unfractionated heparin (UFH) or enoxaparin, or half-dose TNK with abciximab and reduced-dose UFH.

RESULTS

Older patients had a higher risk profile, and lower use of concomitant therapies and revascularization procedures. We found an interaction between age and treatment effect for the efficacy end point (P = .0007) and the efficacy plus safety end point (P < .0001). Younger patients (<65 years) had a lower risk of the composite efficacy plus safety end point with enoxaparin (relative risk [RR] 0.84, 95% CI 0.74-0.94) or abciximab (RR 0.79, 95% CI 0.69-0.90) compared with UFH. In patients >65 years of age, the benefit of enoxaparin appeared to be offset by an increased risk of bleeding complications. The risk of the efficacy plus safety end point tended to be higher in elderly patients receiving abciximab and half-dose TNK (RR 1.18, 95% CI 0.91-1.51 for 76-85 years of age and RR 1.48, 95% CI 0.88-2.49 for >85 years of age).

CONCLUSIONS

Although TNK with either enoxaparin or abciximab appeared to be more effective than with standard UHF in younger patients, these combinations tended to be less effective and even may be unsafe in the elderly. Development of new combination strategies and dosing schemes of fibrinolytics and antithrombotics with improved efficacy and safety in the elderly remains a high priority.

摘要

背景

老年急性心肌梗死患者的死亡和出血并发症风险特别高。这些患者抗栓策略的疗效和安全性仍不明确。

方法

为了更深入了解老年患者抗栓策略的风险和益处,我们研究了ASSENT - 3和ASSENT - 3 PLUS试验中接受替奈普酶(TNK)和普通肝素(UFH)或依诺肝素治疗的ST段抬高型心肌梗死(STEMI)患者,或接受半量TNK联合阿昔单抗及减量UFH治疗的患者。

结果

老年患者风险特征更高,同时使用的辅助治疗和血运重建程序较少。我们发现年龄与疗效终点(P = 0.0007)以及疗效加安全性终点(P < 0.0001)的治疗效果之间存在相互作用。与UFH相比,年轻患者(<65岁)使用依诺肝素(相对风险[RR] 0.84,95%置信区间0.74 - 0.94)或阿昔单抗(RR 0.79,95%置信区间0.69 - 0.90)时,疗效加安全性复合终点风险较低。在65岁以上患者中,依诺肝素的益处似乎被出血并发症风险增加所抵消。接受阿昔单抗和半量TNK治疗的老年患者中,疗效加安全性终点风险趋于更高(76 - 85岁患者RR 1.18,95%置信区间0.91 - 1.51;85岁以上患者RR 1.48,95%置信区间0.88 - 2.49)。

结论

虽然TNK联合依诺肝素或阿昔单抗在年轻患者中似乎比标准UFH更有效,但这些联合用药在老年患者中往往效果较差,甚至可能不安全。开发在老年患者中具有更高疗效和安全性的新型联合策略以及纤溶药物和抗栓药物的给药方案仍然是当务之急。

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