积极治疗无症状的颈动脉狭窄 以降低风险


  September 29, 2008(奥地利维也纳) — 某医学中心一系列无症状颈动脉狭窄(ACS)病患的资料显示,2003年建立的积极治疗制度可以减少血栓形成、较少的微小血栓,也减少颈动脉支架或者手术风险事件。
  
  Robarts研究机构的研究人员使用都卜勒超音波发现,颈动脉血栓的微小血栓有较高风险,当对ACS病患进行比较积极的风险因素管理时,微小血栓与心血管事件显著减少。
  
  主要作者、J. David Spence医师向听众表示,这表示对于无症状的颈动脉狭窄患者来说,治疗首选是积极药物治疗,而非支架或者动脉内膜切除术,不到5%的无症状患者可以从有4%或5%风险的支架或者动脉内膜切除术获利;可以利用有无微小血栓来判断哪里些人可以从治疗中获益。
  
  他向Medscape Neurology & Neurosurgery表示,在美国,相较于有症状的病患,约有半数到三分之二的支架与动脉内膜切除术是用在无症状患者;显示有95%是不需要的。
  
  无症状狭窄的治疗主要是根据Asymptomatic Carotid Atherosclerosis Study(ACAS)于1995年发表的结果,显示动脉内膜切除术将手术整体风险与同侧中风风险从11.0%减少到5.1%(Asymptomatic Carotid Atherosclerosis Study之执行委员会。JAMA 1995;273:1421-1428)。
  
  Spence医师表示,但是,当时无症状之狭窄病患未常规使用高剂量statin类药物,所以我们不应该使用老旧资料来判断现在的手术执行。
  
  Spence医师在第6届世界中风研讨会发表结果。
  
  【治疗动脉】
  Spence医师表示,他在此发表的研究有「两个开端」,首先,他们在1990年开始颈动脉血栓领域的研究,校正广泛的风险因素之后,发现颈动脉栓塞最严重的前四分之一病患,其中风或者死亡风险高3.4倍;此外,这些病患有50%的血栓恶化,这些病患有更高的风险。
  
  他表示,这意味著我们只根据传统风险因素进行治疗、有半数病患治疗失败,所以我们在诊所改变治疗计画为治疗动脉,也就是不管风险因素,积极治疗血栓,目标是逆转血栓;这个治疗改革发生在2003年。
  
  他表示,他们也使用穿颅式都卜勒(TCD)研究无症状颈动脉狭窄患者的微小血栓,并在2005年报告指出,TCD相当可以辨识有风险的病患;90%的病患没有微小血栓,有1%的中风风险,严谨信赖界限为1.01 – 1.36,10%微小血栓者则有15.6%中风风险;Spence医师指出,这表示没有微小血栓的病患无法从血管再造获利,因为他们的风险低于手术或者支架风险。
  
  他们获得大笔资金进行有无微小血栓血块的生物学研究,研究两年后向赞助资金的Heart & Stroke Foundation of Ontario提出报告时,微小血栓消失了;他们假设这个消失结果和开始更积极药物治疗的制度有关,因而在目前的研究检视这些病患的微小血栓与心血管事件的倾向。
  
  【微小血栓与事件减少】
  他们机构追踪的468名无症状颈动脉狭窄病患中,199人在2003年临床实务改变前即已加入,169人在那之后加入;Spence医师指出,全部在开始时都依据国际共识标准检测有微小血栓;去年纳入最后一名研究对象,资料搜集到2008年7月1日。
  
  他表示,我们发现在2003年前有12.6%的病患有微小血栓,2003年之后只有3.7%,所以微小血栓减少了;2003年前,每年的血块恶化比率相当明显,2003年开始积极药物治疗之后,相当低。
  
  他们也研究预防诊所4,328名曾经在1997至2007年间测量血块的病患,以建立血块恶化比率;他们报告指出,血块随著年纪逐步增加,特别是停经之后。年纪越大的族群中,有越多病患因为中风就医,而较少因为高血压,可以想见血块恶化率上升,且居高不下。
  
  他们发现这个比率持续上升到2003年,该年之后停止恶化,且平均值开始下降。积极治疗之后,出现缓解的病患比率也加倍,从25%增加到50%;同时减少了胆固醇、三酸甘油脂、低密度脂蛋白,且增加了高密度脂蛋白,他表示,这些改变是因为积极药物治疗所致。
  
  他表示,大部分的微小血栓显示有相似的倾向,出现微小血栓的第一年有14%中风风险,无血栓者有1.2%风险,几乎所有的事件都发生在追踪后的第一年内。
  
  2003年之前,无症状狭窄病患的第一年中风风险为4%,后来减少到0.8%,而第2年的风险后来减少到几乎没有风险;同样地,心肌梗塞(MI)从积极治疗前的6.5%,减少到之后的0% 。
  
  【有无积极药物治疗之无症状颈脉动狭窄的事件降低分析】

事件

没有微小血栓(%)

有微小写栓(%)

P

2003 年前(%)

2003 年后(%)

P

第 1 年内中风

1.2

14.3

< .0001

4

0.8

.02

第 1 年内 MI

2.4

8.6

.07

6.5

0

.0001

第 1 年内死亡

2.9

12.1

.027

5.1

2

.12


  Spence医师指出,以他的想法,现在一些试验用作为终点的动脉内膜中层厚度(IMT),无法作为此类监测的基准。
  
  他表示,IMT每年的变化约为0.015 mm,而颈动脉超音波的分辨率为0.3 mm,所以个体的改变比率无法逐年测量;另一方面,血块区域每年的改变比率为11 mm2 ,在0.3mm的分辨率下可以测量。
  
  他结论表示,我们的格言是,试著治疗没有测得血块的动脉,就像治疗未测得血压的高血压一样,SPACE 2试验正开始在欧洲进行,将可为此议题提供一些观点,因为它将比较无症状颈动脉狭窄患者之颈动脉内膜切除术和颈动脉支架,但是和其它比较这些方式的试验不同的是,它包括了积极药物治疗组在内。
  
  本研究接受Heart & Stroke Foundation of Ontario、国家健康研究中心、Canadian Institutes of Health Research (CIHR-IRSC)等赞助。
  
  奥地利维也纳,第6届世界中风研讨会:摘要:FC01-02。发表于2008年9月25日。

Low Risk for Events from Asymptomatic Carotid Stenosis With Intensive Medical Therapy

By Susan Jeffrey
Medscape Medical News

September 29, 2008 (Vienna, Austria) — New data from 1 center's series of patients with asymptomatic carotid stenosis (ACS) have shown that institution of intensive medical therapy in 2003 was associated with reduced plaque progression, fewer microemboli, and events to levels below the threshold of risk associated with carotid stenting or surgery.

Researchers at Robarts Research Institute, in London, Ontario, while studying the higher stroke risk associated with microemboli on Doppler ultrasound from carotid plaque, found that microemboli and cardiovascular events declined significantly with more intensive risk-factor management in patients with ACS.

J. David Spence
Dr. J. David Spence

"What this means is that for patients with asymptomatic carotid stenosis, the treatment of choice is intensive medical therapy, not stenting or endarterectomy," lead author J. David Spence, MD, told attendees here. "Less than 5% of asymptomatic patients can possibly benefit from stenting or endarterectomy with risks of 4% or 5%." Those who can benefit can be identified by the presence of microemboli, he said.

In the United States, between half and two-thirds of stenting and endarterectomy procedures are for asymptomatic vs symptomatic patients, he told Medscape Neurology & Neurosurgery. "What we're showing is it's unwarranted in 95% of them."

Treatment of asymptomatic stenosis is based largely on results published in 1995 of the Asymptomatic Carotid Atherosclerosis Study (ACAS), which showed that endarterectomy reduced the aggregate risk of surgery and ipsilateral stroke from about 11.0% to 5.1% in these patients, he said (Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 1995;273:1421-1428).

"But in those days, people weren't using high-dose statins routinely in patients with asymptomatic stenosis," Dr. Spence said. "So we shouldn't be using data that old to justify doing procedures now."

Dr. Spence presented their findings here at the 6th World Stroke Congress.

Treating Arteries

The work he is presenting here has "2 beginnings," Dr. Spence said. In the first, he and colleagues began studying carotid total plaque area in 1990, largely for research purposes, and found that those patients in the top quartile for carotid plaque area had a 3.4-times higher risk for stroke or death after adjustment for a wide variety of risk factors. In addition, 50% of these patients had progression of plaque, and those patients were at higher risk for events.

"What this meant was that we were failing in half our patients, just treating according to traditional treatment of risk factors, so we changed the paradigm in our clinic from treating risk factors to treating arteries," he said. That is, regardless of the risk factors, they intensify therapy in the setting of high plaque burden, with the goal of plaque regression. This change occurred in 2003.

They were also studying microemboli on transcranial Doppler (TCD) in patients with asymptomatic carotid stenosis and in 2005 reported that TCD "perfectly defined the patients at risk," he said. The 90% of patients who had no microemboli had a 1% risk for stroke with tight confidence limits (1.01 – 1.36), and the 10% with microemboli had a 15.6% risk for stroke. "This meant the patients without microemboli cannot benefit from revascularization, because their risk is lower than the risk of surgery or stents," Dr. Spence noted.

He and colleagues obtained grant funding to study the biology associated with plaque with and without microemboli, but 2 years into the study had to report to their funders, the Heart & Stroke Foundation of Ontario, that the microemboli were disappearing. They hypothesized that the decline might be related to the institution of more intensive medical therapy, and in the current study examined secular trends in microemboli and cardiovascular events in their population.

The Decline of Microemboli — and Events

Of 468 patients with asymptomatic carotid stenosis followed at their institution, 199 were studied prior to the shift in practice in 2003, and 169 after. All had baseline microembolus detection by international consensus criteria. The last patients entered were studied for at least a year, Dr. Spence noted, and the database was closed July 1, 2008.

"What we found was that microemboli were present before 2003 in 12.6% of patients, but since 2003, it's only 3.7%, so microemboli had been declining," he said. The annual rate of plaque progression was significant before 2003 and very low after 2003 and the institution of intensive medical therapy.

They also studied 4328 patients from their prevention clinics who had had plaque measurements between 1997 and 2007 to establish the rate of plaque progression. They report that plaque rises steeply with age, particularly after menopause. With an aging population and more patients referred because of stroke and less because of hypertension, he said, "you would expect the rate of plaque progression would be going up and then remain high."

They found the rate did rise, until 2003, when it stopped progressing and they began to see regression on average. The proportion of patients showing regression almost doubled, from 25% to 50%, after the move to intensive therapy. The decline was mirrored by a decline in cholesterol, triglycerides, and low-density lipoprotein and an increase in high-density lipoprotein over the same period, suggesting the changes were due to the intensive medical therapy, he said.

The larger population showed a similar trend in microemboli, showing a 14% risk for stroke in the first year when microemboli were present, and 1.2% without. "Almost all the events occur in the first year of follow-up," he said.

Prior to 2003, the 1-year risk of stroke in patients with asymptomatic stenosis was 4%, he noted, which has declined to 0.8% in the latter period, again with almost no risk seen in year 2. Similarly, myocardial infarction (MI) declined from 6.5% before intensive therapy was introduced to 0% afterward.

Decline in Events Associated with Asymptomatic Carotid Stenosis With and Without Intensive Medical Therapy
Event No Microemboli (%) Microemboli (%) P Before 2003 (%) After 2003 (%) P
Stroke in year 1 1.2 14.3 < .0001 4 0.8 .02
MI in year 1 2.4 8.6 .07 6.5 0 .0001
Death in year 1 2.9 12.1 .027 5.1 2 .12

Dr. Spence noted that in his view, intima-media thickness (IMT), used as an end point now in some trials, cannot provide the basis for this kind of monitoring.

"IMT change annually is around 0.015 mm, and the resolution of carotid ultrasound is 0.3 mm, so the rate of change in an individual cannot be measured from year to year," he said. "On the other hand, the average rate of change of plaque area is 11 mm2 per year, which can readily be measured with a resolution of 0.3 mm.

"So our mantra is trying to treat arteries without

    
相关报导
睾固酮治疗的最初6个月血栓风险最高
2016/12/14 下午 04:39:43
WARP试验结果:Warfarin无法减少使用导管之癌症病患的血栓症
2009/2/23 下午 05:57:00
SPACE、EVA-3S:颈动脉支架或者手术之后的期中中风风险相似
2008/9/18 下午 03:35:00

上一页
   1   2   3   4   5   6  




回上一页