Strategies to limit periprocedural bleeding in percutaneous coronary interventions are effective, particularly in the patients at highest risk for bleeding, according to a report in the June 2 issue of JAMA.

Unfortunately, these strategies are underused, and the very patients most likely to benefit are the least likely to receive them, reported Dr. Steven P. Marso of Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, and his associates.

Targeting bleeding complications “holds great potential for improving the safety and cost-effectiveness of PCI,” since more than 1 million of the procedures are performed in the United States every year and bleeding complications occur in 2%-6% of them. Major bleeding events raise the risks for early and late mortality, MI, and stroke, and also “result in an average 4- to 6-day increase in length of stay and, on average, increase hospital costs by $6,000-$8,000,” the investigators noted.

They studied bleeding complications using the National Cardiovascular Data Registry, a nationwide database of catheterization and PCI procedures at more than 1,100 medical centers in the United States. They assessed data on more than 1.5 million patients who underwent PCI via the femoral artery approach during the period from Jan. 1, 2004, to Sept. 30, 2008.

To mitigate bleeding, vascular closure devices such as Angio-Seal (St. Jude Medical) and Perclose A-T (Abbott Vascular), the drug bivalirudin, or both were used in 24%, 23%, and 18% of patients, respectively. Manual compression, used in 35% of patients, served as the control strategy.

Periprocedural bleeding, the primary outcome for this study, occurred in more than 30,000 patients (2%). This was defined as bleeding that required a blood transfusion or a prolonged hospital stay, or bleeding that was associated with a greater than 3-g/dL decline in hemoglobin level.

Bleeding events occurred in 2.1% of patients in whom vascular closure devices were used, 1.6% who received bivalirudin, and 0.9% who received both preventive strategies. In comparison, bleeding events occurred in 2.8% of patients who received manual compression.

Independently of preprocedural risk of bleeding, vascular closure devices were associated with 6.7 fewer bleeding events per 1,000 patients, bivalirudin was associated with 8.5 fewer events per 1,000, and the combination of both devices and bivalirudin was associated with 14.2 fewer events per 1,000, compared with manual compression.

In a further analysis of the data, patients were stratified according to their estimated risk for bleeding before the procedure began. As bleeding risk increased, differences in actual bleeding rates between the four strategies became more pronounced.

Among the highest-risk patients, “the use of vascular closure devices plus bivalirudin was associated with an absolute 3.8% lower bleeding rate, which translates into an estimated number needed to treat of 33 to prevent 1 bleeding event, as compared with manual compression,” Dr. Marso and his colleagues wrote (JAMA 2010;303:2156-64).

Unfortunately, patients at highest risk for bleeding were the least likely to receive bleeding-control strategies: A total of 40.3% of those patients received manual compression, compared with 30.8% of those with the lowest risk, while 14.4% of the highest-risk patients vs. 21.0% of the lowest risk patients received bivalirudin plus vascular closure.

Translating these study findings into change in clinical practice will be “challenging” for several reasons, the researchers noted.

“First, assessing the risk for bleeding in clinical practice is neither inherently intuitive nor commonly used. Second, physicians have more experience using bivalirudin in lower-risk patients, since it was first studied in patients undergoing elective PCI and only recently in higher-risk patients,” they said.

In addition, some patients are not suited to one or the other of these strategies. Bivalirudin is not recommended in those taking anticoagulants or those who have a chronic total occlusion, and closure devices are not recommended in patients with certain anatomical limitations such as severe calcification or peripheral artery disease.

Dr. Marso and his associates reported receiving support from many sources, including The Medicines Company, maker of bivalirudin, Amylin Pharmaceuticals, Boston Scientific, Volcano Corporation, Terumo Corporation, Abbott Vascular, and NovoNordisk.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

据6月2日发表于《美国医学会杂志》(JAMA)上的一项报道，减少经皮冠状动脉介入治疗(PCI)围手术期出血的策略非常有效，尤其是对于高危出血患者。

 

遗憾的是，这些策略没有被充分利用，受益可能性越大的患者接受这些策略的可能性越小，美国密苏里州堪萨斯市圣·卢克中美洲心脏研究所的Steven P. Marso博士和同事们报道指出。

 

针对出血并发症进行处置“在提高PCI的安全性和成本效益方面有巨大潜力，”因为在美国每年约进行逾100万例手术，而出血并发症的发生率为2%~6%。严重出血事件增加了早期和晚期死亡、心肌梗死(MI)以及卒中的发生风险，也会“导致住院时间平均增加4~6天，医院费用平均增加6,000~8,000美元，”研究者指出。

 

他们应用美国国家心血管数据注册处(NCDR)对出血并发症进行了研究，NCDR是一家全国性数据库，含有美国逾1,100家医学中心与插管和PCI手术有关的数据。他们对2004年1月1日~2008年9月30日间的1,500万例以上经股动脉行PCI术的患者进行了评估。

 

为了减轻出血，分别有24%、23%及18%的患者在术中应用了血管封堵器如Angio-Seal(美国圣犹达医疗公司 )和Perclose A-T(雅培血管部)、药物比伐卢定、或血管封堵器联用比伐卢定。35%的患者采用手法压迫止血，作为试验对照策略。

 

该研究的主要结局是围手术期出血，其发生例数达30,000例以上(2%)。围手术期出血定义为需输血或延长住院时间的出血，或血红蛋白水平下降超过3g/dl的出血。

 

在出血事件的发生率上，应用血管封堵器组为2.1%，比伐卢定治疗组为1.6%，两项预防策略联用组为0.9%。相比之下，接受手法压迫止血组出血事件的发生率为2.8%。

 

如不考虑术前的出血风险，与手法压迫止血相比，应用血管封堵器组出血事件发生率较低，为6.7例/1,000例患者，比伐卢定治疗组为8.5例/1,000例患者，封堵器与比伐卢定联用者为14.2例/1,000例患者。

 

对数据做进一步分析，根据术前估测的出血风险对患者进行分层研究。随着出血风险的增加，这4项策略之间实际出血率的差异也越来越显著。

 

在最高危患者中，“与手法压迫止血相比，血管封堵器联用比伐卢定的出血率降低3.8%(绝对值)，这意味着需要治疗大约33例患者以预防1例出血事件。” Marso博士和同事们写道(JAMA 2010;303:2156-64)。

 

遗憾的是，最高危出血患者采用控制出血策略的可能性最小：这些患者中共有40.3%采用手法压迫，14.4%采用封堵器联合比伐卢定；而在最低危出血患者中有30.8%采用手法压迫，20.1%采用联合策略。

 

由于多种原因，将这些研究结果投入到临床实践中会极具“挑战性”，研究者们说。

 

“首先在临床实践中评估出血风险既不靠个人直觉也未得到普遍应用。其次，对于低危患者，医生们应用比伐卢定的经验更多，因为该药最初是在行择期PCI手术的患者中进行试验，只是最近在高危患者中开展研究，”他们说。

 

除此之外，某些患者也适用这些策略。现不推荐将比伐卢定用于那些服用抗凝剂的患者或那些患有慢性完全闭塞性血管病的患者；另外，也不推荐将封堵器用于有某些解剖结构限制的患者，例如严重钙化或外周动脉病变。

 

Marso博士和同事们的研究获得多方赞助，包括比伐卢定生产厂家——Medicines公司、美国Amylin 制药公司、波士顿科学公司、Volcano公司、泰尔茂公司、雅培公司血管部以及诺和诺德制药有限公司。

 

爱思唯尔  版权所有