“阿司匹林抵抗”增加心血管事件再发风险得到Meta-分析证实

\"Aspirin Resistance\" Raises Risk of Recurrent CV Events, Confirms Meta-Analysis
“阿司匹林抵抗”增加心血管事件再发风险得到Meta-分析证实

August 17, 2007 (Leiden, the Netherlands) - So-called aspirin resistance raises the risk of recurrent cardiovascular events almost four times in patients taking aspirin for secondary prevention, suggests a meta-analysis of a dozen small studies that defined the phenomenon according to a variety of ex vivo tests that directly or indirectly measured platelet reactivity [1].
2007年8月17日荷兰莱顿报道，所谓的阿司匹林抵抗增加心血管事件再发风险差不多四倍于阿司匹林二级预防服用者的报道促成了对12个小型研究进行的Meta-分析，这些研究根据不同的直接或间接测定血小板活性的离体实验来得到了这一结果[1]。

The finding points to a need for further research \"to thoroughly evaluate individual determinants of laboratory aspirin resistance, predictive value of the various laboratory methods, and possible solutions for individual patients,\" write the authors, Dr Jaapjan D Snoep and associates (Leiden University Medical Center, the Netherlands). Their report appears in the August 13/27, 2007 issue of the Archives of Internal Medicine.
作者Jaapjan D Snoep博士及其合作机构-荷兰Leiden大学医疗中心称，这个发现指出需要进一步的研究，对实验室阿司匹林抵抗的个体决定因素，不同实验方法得到的预测值以及合理的个体解决方案做全面的评估。报告刊登在2007年8月13/27日的《内科学文献》上。

Dr Steven R Steinhubl (University of Kentucky, Lexington) told heartwire that he's concerned about the Leiden group's report, as he is about much of the literature on aspirin resistance, for what it doesn't clearly say: that no one knows what, if anything, should be done about it. Such reports may leave the impression that the risk can be lowered by raising the aspirin dose or making other changes to antiplatelet therapy, \"and that is not only unproven, the observational data that we have tell us almost definitively that it's not true.\"
美国莱克星顿肯塔基大学的Steven R Steinhubl博士告诉heartwire，他关注莱顿小组的报道，因为他在收集阿司匹林抵抗方面的文献，但报告没有说清其原因，即使说清了，也没人知道该怎样处理。这些报告可能给人这样的印象：通过增加阿司匹林的剂量或者改用其它抗血小板治疗可降低心血管风险。这一点并未得到证实，而得到的观测数据几乎可以肯定地告诉我们那并不是真的。

If anything, Steinhubl said, the evidence suggests higher aspirin doses increase risk, and the CHARISMA trial suggests that the same happens from adding clopidogrel (Plavix, Sanofi-Aventis), at least in a primary-prevention setting. As previously reported by heartwire, a strong signal of increased risk for cardiovascular death was observed in CHARISMA's patient subgroup with multiple risk factors but no history of CV events.
Steinhubl说，正相反，证据表明增加阿司匹林的剂量会增加心血管风险，CHARISMA试验通过增加氯吡格雷(Plavix, 塞诺菲-安万特)的剂量也得出了同样的结论，至少在一级预防时是这样的。与heartwire之前的报道一样，增加心血管死亡风险的强烈信号在具有多种危险因素但无心血管事件史的CHARISMA患者群中被观察到。

Even the imprecise term \"aspirin resistance\" promotes the idea that it is something to be overcome, according to Steinhubl. He said the phenomenon is more appropriately described as \"increased platelet reactivity while receiving aspirin.\" It may be little more than, for example, a sign that platelets are more active as a response to inflamed endothelium, Steinhubl observed. \"There are many possible reasons that may have absolutely nothing to do with the antiplatelet therapy.\"
用Steinhubl的话来说，恰好是“阿司匹林抵抗”这个模糊不清的称呼促成“it is something to be overcome”（必胜？）的念头。他说，把这说成“吸收阿司匹林的同时增强了血小板的活性”更为恰当。Steinhubl观察到，这也许仅仅表示血小板的活性比对炎症内皮反应更高而已。而且可以得出很多完全与抗血小板治疗无关的推论。

Steinhubl acknowledged the aura of cynicism surrounding the issue of aspirin resistance and allusions that something can and should be done about it. The issue, somewhat notoriously, is seen by many as driven by the availability of commercial tests that reflect platelet reactivity and of patented alternative antiplatelet drugs.
Steinhubl承认围绕阿斯匹林抵抗及“什么可以做”和“什么应该做”的问题的气氛有点玩世不恭。几乎众所周知，被看着是由反映血小板活性的商业试验和新的抗血小板药替代品的利益所驱动。

However, he said, \"I think there's absolutely no role [for measuring aspirin resistance] except in the setting of a clinical trial, even in secondary prevention,because there isn't enough evidence that we would be doing anything for the patient, and there's the potential that we could harm them.\"
然而，他说，“我认为除进行临床试验之外，测定阿司匹林抵抗完全没有作用，即使是在二级预防时。因为没有足够的证据表明应该为患者做些什么，这样做是否会伤害患者。”

The meta-analysis from Snoep and coauthors encompassed 1813 patients with established CV disease from 12 prospective studies that used \"any test that reflects platelet thromboxane A2 synthesis or platelet function\" to identify aspirin resistance and met a range of criteria that included MI, stroke, or other prospectively defined CV outcomes--not necessarily clinical events--as end points.
Snoep及其合作者对来自12个前瞻性研究的1813名确诊的心血管疾病患者数据进行了meta-分析，这些研究使用反映血小板血栓素A2合成或者血小板功能的实验来证明阿司匹林抵抗，并且符合标准范围（包括心肌梗塞、中风以及其它预设为终点的的心血管预后-不一定是临床活动）。

The studies varied in the patients' cardiovascular conditions, aspirin dosages, tests for aspirin resistance, end points, and follow-up time, but nearly all suggested a positive association between aspirin resistance and CV risk, the authors write. The phenomenon's average prevalence in the studies was 27%.
文章的作者说，这些研究在心血管患者的状况、阿司匹林的剂量、阿司匹林抵抗试验、终点以及随访时间上有所不同，但几乎所有的结果都表明阿司匹林与心血管风险正相关。研究过程中出现这种现象的平均几率为27%。

The overall odds ratio for CV events among patients with aspirin resistance was 3.8 (95% CI 2.3-6.1) and appeared independent of aspirin dosage, which ranged from 80 to 325 mg/day. It was 4.4 (2.2-8.7) among the seven studies with clinical-event end points, 2.4 (0.4-14.3) averaged across the three studies with reocclusion after PCI as an end point, and 3.1 (1.6-6.0) for two studies measuring PCI-related myonecrosis.
出现阿司匹林抵抗的患者中心血管事件总优势比为3.8(95%置信区间[2.3，6.1]) 与剂量（80-325mg/天）无关。在7个具有临床事件终点的研究中则为4.4（2.2-8.7），以经皮冠状动脉介入治疗(PCI)后再梗作为终点的3个研究的平均值为2.4(0.4-14.3) ,测量PCI相关肌坏死的2各研究为3.1 (1.6-6.0)。

According to Steinhubl, the analysis serves to show that there's evidence enough \"to do a trial of altering therapy based on some measure of aspirin resistance.\" It should probably be in the context of secondary prevention, for which the benefits of antiplatelet therapy are far more established, he said.
用Steinhubl的话说，分析是为表明“进行根据阿司匹林抵抗测定结果而改变治疗的临床试验有足够的证据”服务的。他说，也许在二级预防试验中是这样，因此抗血小板治疗的获益远多于已明确的那些。

The phase 3 TRITON--TIMI-38 trial comes close to that, he said. Sponsored by Daiichi
Sankyo and Eli Lilly, the soon-to-be-reported study randomized 13 614 patients with ACS in 30 countries to receive clopidogrel or the sponsors' investigational thienopyridine, prasugrel, on top of aspirin in conjunction with PCI. Beyond the clinical events that are the trial's primary efficacy measure, said Steinhubl, who said he wasn't involved in the trial, TRITON is also looking at the relationship of clinical outcomes to the achieved degree of platelet inhibition--if any.
他说，TRITON-TIMI-38 Ⅲ期试验与此相近。即将公布的由第一三共和礼来共同发起的研究将来自30个国家总计13614名急性冠脉综合征患者随机分为三组，在PCI联合阿司匹林治疗的基础上分别服用氯吡格雷（clopidogrel）、实验药物噻吩并吡啶（thienopyridine）、普拉格雷（prasugrel）。并未参与该试验的Steinhubl说，TRITON正在关注临床结果与血小板抑制完成程度之间的关系，即使有的话。（“on top of aspirin in conjunction with PCI”不知该如何翻译）

Snoep et al had no disclosures to report. Steinhubl said he has received honoraria for serving as an advisor to Daiichi Sankyo, Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, The Medicines Company, Portola, and PlaCor.
Snoep等还未公开报告。Steinhubl说，作为第一三共、礼来、勃列斯多·迈耶施贵宝、赛诺菲-安万特，The Medicines Company, Portola, and PlaCor顾问，他已经收到了谢礼。

1.Snoep JD, Hovens MMC, Eikenboom JCJ, et al. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: A systematic review and meta-analysis. Arch Intern Med 2007; 167:1593-1599.