[TCT2007]DESERT 注册试验：DES血栓形成的预测因素分析

Drug-eluting Stent Thrombosis Rate Difficult to Measure

　　波士顿Beth Israel 医疗中心的Donald E Cutlip教授说，DES 血栓形成是冠状动脉DES置入后严重的并发症，但其发生率相对较低且研究较少。队列基础分析需要更多年的随访和更多的研究对象。

　　Cutlip教授说，“问题是DES发生率测定非常困难，原因是没有一个统一的定义。“ARC已经制订了一个能广泛用于未来测定的定义。根据ARC的新定义，明确或已经证实的DES支架血栓有新发急性缺血事件，造影或尸检有支架闭塞或血栓形成的证据；很可能DES支架血栓是30天内不明原因的死亡，或靶血管区域急性心肌梗死无造影或尸检的证据；可能的DES支架血栓包括30天之后任何的难以解释的死亡，可能血栓定义很脆弱，因为长期随访的临床试验中难以解释的死亡很常见。这个定义不可能将支架血栓导致的死亡和其他非心脏性死亡区别开来。

　　临床危险

　　DES血栓定义的重要性在于支架血栓和现实临床事件相关，华盛顿医疗中心心脏主任Ron Waksman教授说根据Waksman等发布的文献回顾，30天时DES血栓相关的死亡率是15－33%，6个月和9个月时分别是31％和45%。Waksman说，“有人顾虑的是再狭窄本身不会增加死亡率和心肌梗死。”

　　Waksman说该注册研究包括了8402例在他的中心应用CYPHER和TAXUS支架治疗的患者，共发现83例DES血栓，127例可疑血栓，每年确定支架血栓发生率0.36％，确定和可能支架血栓发生率0.84％。支架血栓和糖尿病、心肌梗死入院、支架数量和再狭窄病变治疗相关。

　　氯吡格雷的应用并没有消除支架血栓，2年时66%发生支架血栓的患者氯吡格雷应用的依从性良好。“氯吡格雷本身并没有抑制支架血栓形成，因此我们需要开发新的可供选择的策略。”

　　DESERT注册研究

　　Waksman和Martin Leon教授将于2007年11月发起药物洗脱支架血栓事件注册研究（DESERT），该研究将收集DES血栓形成的预测因素资料，样本量足够大并采用有效的病例对照研究设计。

　　纳入该注册研究的中心必须要每年完成1000例PCI，入选前一年至少发生3例晚期支架血栓事件。Waksman说“总共要有500例事件，我们就能分析25－50个可能预测因子的效应。”

　　（武警总医院　韩玮　编译）

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Drug-eluting Stent Thrombosis Rate Difficult to Measure

DESERT registry will collect data to determine the predictors of DES thrombosis.

Drug-eluting stent thrombosis is the most devastating complication of coronary DES implantation, but it is a relatively new and poorly studied phenomenon. Cohort-based analyses require years of follow-up and a large number of patients, according to Donald E. Cutlip, MD, a cardiologist at the Beth Israel Deaconess Medical Cen¬ter in Boston.

“The problem with measuring the rate of drug-eluting stent thrombosis is that there is no standardized definition,” Cutlip said. The Academic Research Consortium (ARC) has developed a definition that could provide a gold standard for future measurement, he added.

Under the ARC defi¬nition, a “definite/confirmed” DES thrombosis would be a new acute ischemic event with angiographic or autopsy evidence of stent occlusion or thrombosis. A “probable” DES thrombosis would be unexplained death within 30 days, unless it was an AMI trial, or target vessel MI without angiography or evidence of another culprit.

“Possible” DES thrombosis would include any unexplained death beyond 30 days. “The ‘possible’ stent thrombosis definition is still weak because late unexplained death is common in clinical trials during long-term follow-up. Applying this definition liberally is unlikely to distinguish real events related to stent thrombosis from other causes, including noncardiac,” Cutlip said.

Clinical risk

A definition of DES thrombosis is important because the condition has been associated with real clinical events, according to Ron Waksman, MD, associate chief of Cardiology at the Washington Hospital Center in Washington, D.C. According to a literature review presented by Waksman, at 30 days, the mortality rate associated with DES thrombosis is 15% to 33%; at 6 months, 31%; at 9 months, 45%.

“This is concerning because restenosis itself has never been associated with higher mortality or MIs,” Waksman said.

Waksman said the registry at his institution included 8,402 patients who were treated with Cypher (Cordis, Johnson & Johnson), Taxus (Boston Scientific), or both. He and his colleagues observed DES thrombosis in 83 patients and possible stent thrombosis in 127 patients. The incidence rate was 0.36% per year for definite stent thrombosis and 0.84% per year for definite and probable stent thrombosis combined. Stent thrombosis was linked with diabetes mellitus, MI admission, number of stents, and presence of a restenotic lesion.

Use of clopidogrel (Plavix, Bristol-Myers Squibb) did not eliminate stent thrombosis. At 2 years, 66% of the patients who had developed stent thrombosis had been clopidogrel-compliant (Figure). “Clopidogrel itself is not prohibitive of stent thrombosis, so we may have to come up with an alternative strategy,” Waksman said.

DESERT registry

Waksman and Martin Leon, MD, chairman emeritus of CRF, will launch the Drug-eluting Stent Event Registry of Thrombosis (DESERT) in November 2007. The registry will collect data to describe the predictors of DES thrombosis, using an adequately sized and powered case-control study design.

To be eligible, a center must perform 1,000 PCI procedures per year and have demonstrated an occurrence of at least three late-stent thromboses in the previous year. “Given 500 total events, we should be able to adequately assess the effects of between 25 to 50 potential predictors,” Waksman said.