专家视点：非STEMI治疗的新进展

科罗拉多州斯诺马斯——一项涉及近100万例80岁以上的非ST段抬高性心肌梗死(NSTEMI)患者的研究显示，一种早期积极策略对此类患者尤其有益。

高龄NSTEMI患者以往并未得到充分研究，对于此类患者，临床上常规首选保守治疗。


David R. Holmes, Jr.医生

罗切斯特梅奥医院的David R. Holmes Jr.医生在斯诺马斯心血管年会上评论指出：“这是一项重要的研究。我们可以看到，当你日益衰老时罹患冠状动脉疾病的风险会逐渐增加，在其他因素都不变的情况下，采用积极策略很可能会有更好的效果。”

这项研究纳入了2003~2010年间968,542例80岁以上的NSTEMI住院患者。83%的患者初始接受保守治疗，即仅在发生血液动力学或心电不稳定事件、最佳药物治疗情况下仍发生难治性心绞痛，或者检测结果提示高风险时才接受冠脉造影。另外17%的患者接受早期积极处理，即在入院后48小时内接受冠脉造影。

在80岁以上高龄患者中，接受早期积极策略处理者倾向于更年轻、肥胖、吸烟、血质紊乱、高血压、白人和男性，而且更可能有已知的血管疾病。校正潜在混杂因素的多变量分析显示，早期积极策略组的院内死亡率比保守治疗组降低了34%，消化道岀血风险降低了37%，平均住院时间缩短了半天。不过，早期积极策略组患者的心源性休克风险升高了1.1倍(Am. J. Med. 2013;126:1076-83)。

进入心导管室的时间是否重要？

近期另一项研究分析了在积极策略中将NSTEMI患者送进心导管室的最佳时间框架。这是一篇基于7项随机对照试验、5,370例NSTEMI患者和4项观察性研究、77,000多例NSTEMI患者的的meta分析。其结论是：迄今尚无有力证据表明时间间隔对结局有显著影响(Ann. Intern. Med. 2013;158:261-70)。

Holmes医生指出：“现有的数据就是如此。只要能把患者送进心导管室就行了，不论是2小时内、6小时内还是18小时内都没有太大关系。这对于医疗系统有着重要启示。假如1例患者在周五晚上来到医院，或许你不必急着当晚就把这例患者送进心导管室，而是可以等到第二天甚至等到周一早上医疗团队成员到齐后再实施心导管术。”

GRACE和CRUSADE

在选择对NSTEMI患者采取积极或保守策略时，制定决策的基石涉及对正式风险评分的使用。如今又太多的风险评分系统正在被使用。哪一种是最适合心内科医生使用的呢？一篇纳入36项研究、近117,000例NSTEMI患者的meta分析显示，GRACE(全球急性心脏事件注册)风险评分(JAMA 2004;291:2727-33)是最佳选择之一。该评分系统显著优于目前也在被广泛使用的TIMI评分以及其他相对不知名的评分系统(Contemp. Clin. Trials 2012:33:507-14)。目前，Grace评分的手机应用程序也已上线。

尽管临床医生往往在NSTEMI病程早期就能作出诊断和开始治疗(这在很大程度上是因为肌钙蛋白检测在急诊科得到了广泛应用)，但NSTEMI的远期并发症和死亡风险仍然较高，尤其是在老年患者中。纳入19,336例接受早期心导管术、年龄≥65岁的NSTEMI患者的CRUSADE(早期应用ACC/AHA指南对不稳定型心绞痛患者快速风险分层能否减少不良结局)注册研究便凸显了这一点。

21%的患者仅接受了药物治疗，60.8%的患者接受了经皮冠脉介入治疗(PCI)，18.2%的患者接受了冠脉旁路移植术(CABG)。结果显示，这三组患者的5年未校正全因死亡率分别为50%、33.5%和24.2%。未校正5年死亡、MI再入院或卒中再入院复合终点发生率分别为62.4%、44.9%和33%。研究者总结称，通过CABG或PCI接受再血管化治疗的老年NSTEMI患者具有更好的远期结局。今后的临床试验应在这一结论的基础上进行(Circ. Cardiovasc. Qual. Outcomes 2013;6:323-32)。

Holmes医生指出，在过去20年间，STEMI发病率逐渐下降，而NSTEMI发病率则持续上升。不仅是美国，全世界都是这样。例如在澳大利亚，1993~2010年间校正后NSTEMI发病率猛增215%，从67例/10万人年增至182例/10万人年，而与此同时STEMI发病率降低了30%。“显然，NSTEMI已经成了所有心内科医生都必须处理的疾病。随着人口老龄化，NSTEMI增长率还会进一步上升。”

Holmes医生报告称无相关利益冲突。

专家点评：反思目前的NSTEMI治疗策略

这些研究共同为NSTEMI积极治疗策略中的关键环节提供了指导，即年龄因素、时机的影响和风险分层评分。目前，“少即是多”原则常被用于80岁以上高龄患者，然而大样本量注册数据显示，即使在校正混杂因素之后，积极治疗仍能在一系列结局指标上带来获益。因此，我们应当重新审视临床上的现行做法。尽管既往研究确定了积极策略中的时机，但上文中的meta分析告诉我们，只要能完成心导管术即可，具体的实施时间其实与NSTEMI结局无关，这是一个非常重要的结论。

最后，尽管多数机构都在使用TIMI评分系统，但GRACE评分的表现更佳，这是一个令人意外的发现。

总而言之，我们应当在这些关键研究的基础上开展随机对照试验，从而为有关NSTEMI患者的重要问题找出确切答案。

点评专家Hiren Shah医生是美国西北大学Feinberg医学院的助理教授，西北纪念医院内科与心脏遥感住院医师单元的主任。他还担任了《Hospitalist News》的编委。

爱思唯尔版权所有  未经授权请勿转载

By: BRUCE JANCIN, Cardiology News Digital Network

SNOWMASS, COLO. – An early invasive strategy is particularly beneficial in octogenarians with non–ST-segment elevation myocardial infarction, according to a recent study involving close to 1 million NSTEMI patients aged 80 years or older.

The very eldest are an understudied segment of the NSTEMI population, for whom an initial conservative strategy has been the dominant approach in daily practice.

"This is an important study. We can see that as you get older and older, by virtue of the fact that you have more and more coronary disease, probably you’re going to be better off with an invasive strategy, all other things being equal," Dr. David R. Holmes Jr. commented in highlighting the study at the Annual Cardiovascular Conference at Snowmass.

The study included 968,542 octogenarians hospitalized with NSTEMI during 2003-2010 and entered into the Nationwide Inpatient Sample. Eighty-three percent were managed via an initial conservative approach, with coronary angiography performed only in the event of hemodynamic or electrical instability, refractory angina despite optimal medical therapy, or a test result indicative of high risk. The other 17% underwent an early invasive approach, with angiography within 48 hours of presentation.

Octogenarians managed via an early invasive strategy were more often younger, obese, smokers, dyslipidemic, hypertensive, white, and male, and more likely to have known vascular disease. In a multivariate analysis adjusted for potential confounders, the early invasive strategy group had a 34% reduction in in-hospital mortality compared with the conservatively managed group. They also had a 37% lower rate of acute ischemic stroke, a 40% reduction in intracranial hemorrhage, a 37% lower risk of gastrointestinal bleeding, and a shorter length of stay by an average of half a day. On the other side of the ledger, they had a 2.1-fold increased rate of cardiogenic shock (Am. J. Med. 2013;126:1076-83).

Does time to cath lab matter?

Another recent study looked at the optimal time frame for taking an NSTEMI patient to the cardiac catheterization laboratory as part of an invasive strategy. This was a meta-analysis of seven randomized controlled trials totaling 5,370 NSTEMI patients, along with four observational studies with more than 77,000 NSTEMI patients. The conclusion: There is as yet no persuasive evidence that the time interval makes a difference in outcomes (Ann. Intern. Med. 2013;158:261-70).

"That’s the data that’s available. It doesn’t matter how quickly you get the patient to the cath lab within that first period of time. You just need to take them, whether it’s in 2 hours, 6 hours, or 18 hours," Dr. Holmes said.

This has important implications as we think about systems of care. If somebody comes into the hospital late on a Friday night, do you have to take them to the cath lab Friday night, or can you wait electively and take them tomorrow or potentially even Monday morning when everybody’s there?" commented Dr. Holmes, professor of medicine at the Mayo Clinic in Rochester, Minn.

GRACE and CRUSADE

The cornerstone of decision making as to whether to opt for an invasive versus a conservative strategy in a given NSTEMI patient involves application of a formal risk score. A plethora of these risk scoring systems are in use today. Which is the best choice for a cardiologist as an aid to decision making? A meta-analysis involving 36 studies with nearly 117,000 NSTEMI patients has concluded that the GRACE (Global Registry of Acute Cardiac Events) risk score (JAMA 2004;291:2727-33) is the best of the pack. It significantly outperformed the TIMI score, which is the other widely used scoring system, as well as others less widely known (Contemp. Clin. Trials 2012:33:507-14).

"GRACE looks like it performs better. We’ll need better ones in the future, of course. But at the present time, select GRACE for risk stratification," advised the cardiologist, adding that a Grace score app is available.

Despite the fact that physicians are diagnosing and treating NSTEMI earlier in its course, in large part because of the widespread use of troponin assays in the emergency department, NSTEMI is still associated with substantial long-term morbidity and mortality, particularly in the elderly. This was underscored in a recent analysis of 19,336 NSTEMI patients aged 65 years or older who underwent early catheterization and were included in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines) registry.

Twenty-one percent of patients received medical management alone, 60.8% underwent percutaneous coronary intervention, and 18.2% had coronary artery bypass graft surgery. The 5-year unadjusted all-cause mortality rate was 50% in the medically managed group, 33.5% in older patients who underwent PCI, and 24.2% in those who underwent CABG surgery. The unadjusted 5-year rate of a composite of death, readmission for MI, or readmission for stroke was 62.4% with medical management, 44.9% with PCI, and 33% with CABG. The investigators concluded that long-term outcomes in elderly NSTEMI patients appear to be better in this large registry when revascularization is accomplished via CABG than with PCI. This sets the stage for future confirmatory trials (Circ. Cardiovasc. Qual. Outcomes 2013;6:323-32).

Dr. Holmes noted that the incidence of NSTEMI has climbed steadily while that of STEMI has declined over the past couple of decades, not just in the United States but worldwide. In Australia, for example, during 1993-2010 the adjusted incidence of NSTEMI increased by a whopping 315%, from 67 to 182 cases per 100,000 person-years, while the adjusted incidence of STEMI fell by 30% (Am. J. Cardiol. 2013;112:169-73).

"NSTEMI is clearly an annuity for all of cardiology," Dr. Holmes said. "The growth rate is increasing and it will continue to increase as we get older."

He reported having no conflicts of interest.

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Rethinking current practice for NSTEMI

These studies collectively offer guidance in key management decisions for an invasive strategy for our NSTEMI patients, namely, the factor of age, the impact of timing, and risk stratification scores. Currently, the "less is more" approach is often taken for octogenarians, but a large sample size from this registry shows better results across a spectrum of outcomes even while adjusting for cofounders. This should prompt a reevaluation of current practice. Although the timing of an invasive approach in STEMI is defined in prior studies, this large meta-analysis tells us that timing in NSTEMI does not correlate with outcomes as long as angiography is pursued at some point in time, a very important conclusion.

Finally, although TIMI scoring systems are used at most institutions, the GRACE score performed even better, a surprising finding.

Taken in sum, these key studies should be followed up by randomized controlled trials to definitively answer these important questions for our NSTEMI patients.

Dr. Hiren Shah is an assistant professor of medicine in the Feinberg School of Medicine, Northwestern University, Chicago, and a medical director of the Medicine and Cardiac Telemetry Hospitalist Unit at Northwestern Memorial Hospital. He is on the advisory board of Hospitalist News.