LMWH preferable to UFH in PCI?

　　巴黎，法国－综合多个随计研究结果的回顾分析发现，与UFH相比在PCI术中静脉应用LMWH能够明显减少严重出血事件，同时并不增加缺血终点事件发生率。

　　这一由Raphaelle Dumaine医生（Pitie Salpetriere医院，巴黎，法国）领导的小组进行的回顾分析发表在2007年12月10/24日出版的Archives of Internal Medicine杂志上。他们在文章中提到，UFH在PCI术中应用受到很多限制，其中包括UFH自身难以预测的稳定性、需要密切监测抗凝水平和缺少被广泛公认的目标抗凝水平。另外，UFH还具有引发vWF因子释放的促凝作用，这将会造成药物中断后的血小板激活和凝血酶的反弹性增加。但是，尽管存在种种限制，UFH依然被在PCI术中得到广泛应用。

　　相比下，LMWH具有更易把握的药理学特性，不需要监测，而且较少引起vWF因子的释放从而减少血小板的激活，与UFH相比更能抑制凝血酶的产生，能够促进组织因子途径抑制物的释放，而且肝素诱导血小板减少的发生率更低。

　　Dumaine医生等解释道，当一些随机研究试图评价与UFH相比LMWH在PCI术中应用的安全有效性时，研究规模通常太小无法在死亡或心梗的效果上得出任何确定的结论。而其中最大的研究―STEEPLE研究，由于研究中发生的缺血事件很少，其结论的效能是有限的。所以他们对13个比较静脉应用UFH和LMWH的随机研究进行meta分析。共包括7318例患者，其中4021例患者（57.4％）接受了LMWH治疗，3117例患者（42.6％）接受了UFH治疗。这一meta分析中了STEEPLE研究，占其中总病例数的约50％。

　　结果显示，与UFH相比使用LMWH能够明显减少严重出血并发症，同时在死亡、心梗或紧急再血管化治疗上无明显差异。

比较PCI术中LMWH和UFH应用的meta分析：主要结果
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终点事件 　　　　　　　　　HR for LMWH vs UFH (95% 可信限)  　　　　　　p 值
严重出血事件  　　　　　　　　0.57 (0.40-0.82) 　　　　　　　　　　　　　0.002
轻微出血事件  　　　　　　　　0.75 (0.47-1.20) 　　　　　　　　　　　　　0.24
死亡/心梗  　　　　　　　　　　0.99 (0.79-1.24) 　　　　　　　　　　　　　0.93
死亡 　　　　　　　　　　　　1.26 (0.57-2.81) 　　　　　　　　　　　　　0.57
心梗 　　　　　　　　　　　　0.97 (0.77-1.22) 　　　　　　　　　　　　　0.79
紧急再血管化治疗  　　　　　　1.30 (0.97-1.75) 　　　　　　　　　　　　　0.08
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　　Dumaine医生等人在文章中指出，虽然PCI技术得到了改进，但出血依然是PCI的一个常见而且代价很大的并发症（发生率在3－10%），它不仅会会造成患者住院时间的延长、疼痛和不适，而且还会增加患者近期和远期的死亡率。大部分的严重出血的患者都需要输血治疗，这是接受PCI治疗的急性冠脉综合征患者远期死亡率的独立风险预测因子。

　　他们还补充道，静脉应用LMWH与UFH相比能够减少严重出血率，这具有重要临床意义，在确定PCI术中应用哪种抗凝剂时应该被考虑到。

　　他们认为这一meta分析在LMWH和UFH预防缺血事件的差距上具有充足的统计学效力。UFH在PCI术中应用没有经过安慰剂对照研究的验证，FDA并没有批准它在PCI术中应用，所以很难确定治疗效果的非劣性指标。但是研究者补充道：“死亡或心梗的OR值小于1和其95%可信限的上限低于1.25将支持UFH和LMWH在预防缺血事件上等效的假设。”

　　作者指出，与UFH相比应用LMWH治疗心梗虽然有更好地疗效，但是会增加出血风险，这与它在PCI术中的情况正好是相反的。这可能与LMWH不同的给药方式有关－在急性冠脉综合征研究中是多次皮下注射给药，在PCI术中是单次静脉注射给药。

       （北京安贞医院　苑飞　编译）

　　（来源：www.theheart.org）

LMWH preferable to UFH in PCI?

December 17, 2007  
Sue Hughes

Paris, France - The use of intravenous low-molecular-weight heparin (LMWH) during PCI is associated with a significant reduction in major bleeding events compared with unfractionated heparin (UFH), without compromising outcomes on hard ischemic end points, a new review of randomized trials concludes .

The review, published in the December 10/24, 2007 issue of the Archives of Internal Medicine, was conducted by a group led by Dr Raphaelle Dumaine (Hôpital Pitie Salpetriere, Paris, France). They note that during PCI, the use of UFH is limited by its unpredictable stability, the need for close monitoring of anticoagulation levels, and the absence of well-determined target anticoagulation levels. In addition, UFH exhibits prothrombotic properties related to poor control of von Willebrand factor release, as well as platelet activation and rebound of thrombin generation after discontinuation. But despite these limitations, UFH remains widely used during PCI.

In contrast, LMWHs have a more predictable pharmacological profile, removing the need for monitoring, and they are also associated with less induction of von Willebrand factor release and reduced platelet activation, a greater inhibition of thrombin generation compared with UFH, enhanced release of tissue factor pathway inhibitor, and a lower incidence of heparin-induced thrombocytopenia, the authors report.

Dumaine et al explain that while several randomized studies have sought to assess the efficacy and safety of LMWH during PCI compared with UFH, they have generally been too small to allow any definite conclusions on the effect on death or MI. And the largest such study—STEEPLE—had a relatively low number of ischemic events, so its power was limited. They therefore conducted the present meta-analysis of 13 randomized studies comparing the intravenous administration of LMWH vs UFH in 7318 patients undergoing PCI. A total of 4201 patients (57.4%) received LMWH, and 3117 patients (42.6%) received UFH. This meta-analysis included the STEEPLE trial, which accounted for approximately 50% of the patients.

Results showed that LMWH use was associated with a significant reduction in the risk of major bleeding compared with UFH, with no significant differences shown in death, MI, or urgent revascularization.

LMWH vs UFH in PCI meta-analysis: Major results 
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End point                 　　HR for LMWH vs UFH (95% CI)  　　　　　　　　　p
Major bleeding  　　　　　　　0.57 (0.40-0.82) 　　　　　　　　　　　　0.002
Minor bleeding  　　　　　　　0.75 (0.47-1.20) 　　　　　　　　　　　　0.24
Death/MI  　　　　　　　　　　0.99 (0.79-1.24) 　　　　　　　　　　　　0.93
Death  　　　　　　　　　　　1.26 (0.57-2.81)　　　　　　　　　　　　 0.57
MI  　　　　　　　　　　　　　0.97 (0.77-1.22) 　　　　　　　　　　　　0.79
Urgent revascularization  　　　1.30 (0.97-1.75) 　　　　　　　　　　　　0.08
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Dumaine et al note that despite the improvement of procedural techniques, bleeding remains a common and costly complication of PCI (occurring in 3% to 10% of patients) and often results in increases in length of hospital stay, patient pain and discomfort, and short- and long-term mortality. Moreover, a large proportion of major bleeds require transfusion, which has been shown to be an independent risk factor for long-term mortality in ACS patients undergoing PCI, they point out.

They add: "The finding that intravenous LMWH is associated with reduced major bleeding rates compared with UFH is of clinical importance and should be considered when determining the appropriate anticoagulation regimen for use during PCI."

They say that this meta-analysis provides enough statistical power to detect differences between LMWH and UFH in the prevention of ischemic events. They point out that there have been no placebo-controlled trials of UFH in PCI, and UFH does not have FDA approval for this indication, so it is difficult to define a noninferiority margin for the treatment effect. But they add: "An OR for death or MI below 1 and an upper limit of the 95% CI below 1.25 supports the hypothesis that UFH and LMWH are equally effective to prevent ischemic events."

The authors point out that use of LMWH for the treatment of MI is associated with improved efficacy but an increased risk for bleeding compared with UFH, which is the opposite of its effects in PCI. They suggest that the reason for this discrepancy may be the different modes of administration of LMWH in the different indications—multiple subcutaneous injections in ACS trials vs a single intravenous injection in PCI trials.

责任编辑    刘瑞琦