Spence醫師指齣以他的想法積極治療無癥狀的頸動脈狹窄以降低風險

發表日期 2008-10-07T06:51:04+08:00

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趣味新聞網記者特別報導 : Spence醫師指齣，以他的想法，現在一些試驗用作為終點的動脈內膜中層厚度(IMT)，無法作為此類監測的基準。　　　　他錶示，IMT每年的變化約為0.015 mm，而頸動脈超 ... 積極治療無癥狀的 .....

作者：Susan Jeffrey

齣處：WebMD醫學新聞

September 29, 2008(奧地利維也納) — 某醫學中心一係列無癥狀頸動脈狹窄(ACS)病患的資料顯示，2003年建立的積極治療製度可以減少血栓形成、較少的微小血栓，也減少頸動脈支架或者手術風險事件。

Robarts研究機構的研究人員使用都蔔勒超音波發現，頸動脈血栓的微小血栓有較高風險，當對ACS病患進行比較積極的風險因素管理時，微小血栓與心血管事件顯著減少。

主要作者、J. David Spence醫師嚮聽眾錶示，這錶示對於無癥狀的頸動脈狹窄患者來說，治療首選是積極藥物治療，而非支架或者動脈內膜切除術，不到5%的無癥狀患者可以從有4%或5%風險的支架或者動脈內膜切除術獲利；可以利用有無微小血栓來判斷哪些人可以從治療中獲益。

他嚮Medscape Neurology & Neurosurgery錶示，在美國，相較於有癥狀的病患，約有半數到三分之二的支架與動脈內膜切除術是用在無癥狀患者；顯示有95%是不需要的。

無癥狀狹窄的治療主要是根據Asymptomatic Carotid Atherosclerosis Study(ACAS)於1995年發錶的結果，顯示動脈內膜切除術將手術整體風險與同側中風風險從11.0%減少到5.1%(Asymptomatic Carotid Atherosclerosis Study之執行委員會。JAMA 1995;273:1421-1428)。

Spence醫師錶示，但是，當時無癥狀之狹窄病患未常規使用高劑量statin類藥物，所以我們不應該使用老舊資料來判斷現在的手術執行。

Spence醫師在第6屆世界中風研討會發錶結果。

【治療動脈】
Spence醫師錶示，他在此發錶的研究有「兩個開端」，首先，他們在1990年開始頸動脈血栓領域的研究，校正廣泛的風險因素之後，發現頸動脈栓塞最嚴重的前四分之一病患，其中風或者死亡風險高3.4倍；此外，這些病患有50%的血栓惡化，這些病患有更高的風險。

他錶示，這意味著我們隻根據傳統風險因素進行治療、有半數病患治療失敗，所以我們在診所改變治療計畫為治療動脈，也就是不管風險因素，積極治療血栓，目標是逆轉血栓；這個治療改革發生在2003年。

他錶示，他們也使用穿顱式都蔔勒(TCD)研究無癥狀頸動脈狹窄患者的微小血栓，並在2005年報告指齣，TCD相當可以辨識有風險的病患；90%的病患沒有微小血栓，有1%的中風風險，嚴謹信賴界限為1.01 – 1.36，10%微小血栓者則有15.6%中風風險；Spence醫師指齣，這錶示沒有微小血栓的病患無法從血管再造獲利，因為他們的風險低於手術或者支架風險。

他們獲得大筆資金進行有無微小血栓血塊的生物學研究，研究兩年後嚮贊助資金的Heart & Stroke Foundation of Ontario提齣報告時，微小血栓消失瞭；他們假設這個消失結果和開始更積極藥物治療的製度有關，因而在目前的研究檢視這些病患的微小血栓與心血管事件的傾嚮。

【微小血栓與事件減少】
他們機構追蹤的468名無癥狀頸動脈狹窄病患中，199人在2003年臨床實務改變前即已加入，169人在那之後加入；Spence醫師指齣，全部在開始時都依據國際共識標準檢測有微小血栓；去年納入最後一名研究對象，資料蒐集到2008年7月1日。

他錶示，我們發現在2003年前有12.6%的病患有微小血栓，2003年之後隻有3.7%，所以微小血栓減少瞭；2003年前，每年的血塊惡化比率相當明顯，2003年開始積極藥物治療之後，相當低。

他們也研究預防診所4,328名曾經在1997至2007年間測量血塊的病患，以建立血塊惡化比率；他們報告指齣，血塊隨著年紀逐步增加，特彆是停經之後。年紀越大的族群中，有越多病患因為中風就醫，而較少因為高血壓，可以想見血塊惡化率上升，且居高不下。

他們發現這個比率持續上升到2003年，該年之後停止惡化，且平均值開始下降。積極治療之後，齣現緩解的病患比率也加倍，從25%增加到50%；同時減少瞭膽固醇、三酸甘油脂、低密度脂蛋白，且增加瞭高密度脂蛋白，他錶示，這些改變是因為積極藥物治療所緻。

他錶示，大部分的微小血栓顯示有相似的傾嚮，齣現微小血栓的第一年有14%中風風險，無血栓者有1.2%風險，幾乎所有的事件都發生在追蹤後的第一年內。

2003年之前，無癥狀狹窄病患的第一年中風風險為4%，後來減少到0.8%，而第2年的風險後來減少到幾乎沒有風險；同樣地，心肌梗塞(MI)從積極治療前的6.5%，減少到之後的0% 。

【有無積極藥物治療之無癥狀頸脈動狹窄的事件降低分析】

事件	沒有微小血栓(%)	有微小寫栓(%)	P	2003 年前(%)	2003 年後(%)	P
第 1 年內中風	1.2	14.3	< .0001	4	0.8	.02
第 1 年內 MI	2.4	8.6	.07	6.5	0	.0001
第 1 年內死亡	2.9	12.1	.027	5.1	2	.12

Spence醫師指齣，以他的想法，現在一些試驗用作為終點的動脈內膜中層厚度(IMT)，無法作為此類監測的基準。

他錶示，IMT每年的變化約為0.015 mm，而頸動脈超音波的解析度為0.3 mm，所以個體的改變比率無法逐年測量；另一方麵，血塊區域每年的改變比率為11 mm2 ，在0.3mm的解析度下可以測量。

他結論錶示，我們的格言是，試著治療沒有測得血塊的動脈，就像治療未測得血壓的高血壓一樣，SPACE 2試驗正開始在歐洲進行，將可為此議題提供一些觀點，因為它將比較無癥狀頸動脈狹窄患者之頸動脈內膜切除術和頸動脈支架，但是和其他比較這些方式的試驗不同的是，它包括瞭積極藥物治療組在內。

本研究接受Heart & Stroke Foundation of Ontario、國傢健康研究中心、Canadian Institutes of Health Research (CIHR-IRSC)等贊助。

奧地利維也納，第6屆世界中風研討會：摘要：FC01-02。發錶於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.

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 measuring plaque is like trying to treat hypertension without measuring blood pressure," he concluded.
The SPACE 2 trial, just getting under way in Europe, will provide some insight into this issue, as it is comparing carotid endarterectomy with carotid stenting in patients with asymptomatic carotid stenosis, but unlike other trials comparing these modalities in asymptomatic patients, it includes an intensive-medical-therapy group.
The study was funded by the Heart & Stroke Foundation of Ontario, the National Institutes of Health, and the Canadian Institutes of Health Research (CIHR-IRSC).
6th World Stroke Congress, Vienna, Austria: Abstract FC01-02. Presented September 25, 2008.

[ 本帖最後由 goodcat1111 於 2008-10-7 13:06 編輯 ]

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