達(dá)拉斯——美國心臟協(xié)會(huì)（AHA）2013科學(xué)年會(huì)上報(bào)告的一項(xiàng)中國隨機(jī)對(duì)照研究結(jié)果顯示，立即采取降壓治療并不能降低高血壓型急性缺血性腦卒中患者14天后的死亡率和殘疾率，不過這一策略是安全的，不會(huì)使患者結(jié)局惡化。該研究結(jié)果同時(shí)在線發(fā)表在《美國醫(yī)學(xué)會(huì)雜志》上。

    美國杜蘭大學(xué)流行病學(xué)教授何江博士報(bào)告稱，中國急性缺血性腦卒中降壓試驗(yàn)（CATIS）結(jié)果表明，對(duì)于收縮壓介于140——219mmHg的相對(duì)輕度缺血性腦卒中患者，是否采取降壓治療應(yīng)因人而異。

    研究者認(rèn)為，缺血性腦卒中發(fā)作后隨即出現(xiàn)的血壓升高是出血轉(zhuǎn)化或腦水腫的風(fēng)險(xiǎn)因素，但也可能促使更多的血液進(jìn)入卒中部位周圍半影區(qū)從而起到保護(hù)作用。降壓措施不適合于再灌注治療患者，但對(duì)于血壓明顯升高（通常定義為收縮壓≥220mmHg）的患者則被認(rèn)為是必須的。

    今年早些時(shí)候公布的美國卒中診治指南指出，對(duì)于不太嚴(yán)重動(dòng)脈高血壓（嚴(yán)重程度在這項(xiàng)試驗(yàn)范圍之內(nèi)）采取降壓治療的推薦依據(jù)存在爭議，動(dòng)脈高血壓治療對(duì)急性缺血性腦卒中患者的受益尚不十分確定（Stroke2013;44:870-947）。但部分美國醫(yī)生對(duì)缺血性腦卒中患者采取適度降壓措施，特別是對(duì)于收縮壓達(dá)到或接近200mmHg的患者。

    基于這項(xiàng)新的研究結(jié)果，克利夫蘭Case醫(yī)學(xué)中心卒中與腦血管中心主任、神經(jīng)學(xué)教授CathySila博士提出了一項(xiàng)針對(duì)未接受再灌注治療、卒中15小時(shí)后收縮壓為140——219mmHg且無大血管狹窄或阻塞的輕度缺血性腦卒中患者的治療策略。她建議，合理的目標(biāo)是在治療最初24小時(shí)內(nèi)血壓降低10——15%,此后7日內(nèi)目標(biāo)血壓<140/90mmHg.

    CATIS納入了中國26家醫(yī)院的4,071例年齡≥22歲、未接受再灌注治療的缺血性腦卒中確診患者。平均年齡62歲，平均就診時(shí)間為卒中發(fā)作后15小時(shí)，中位NIH卒中量表評(píng)分為4.

    2,038例患者隨機(jī)接受降壓治療，靜注血管緊張素轉(zhuǎn)化酶抑制劑依那普利作為一線治療，鈣離子通道阻滯劑和利尿劑分別作為二線和三線治療。目標(biāo)為最初24小時(shí)內(nèi)收縮壓下降10——25%,7日后血壓<140/90mmHg.

    降壓治療效果明顯，治療組24小時(shí)血壓平均下降13%（平均降幅22mmHg），7日后平均收縮壓為137mmHg,而對(duì)照組24小時(shí)血壓平均下降7%（平均降幅13mmHg），7日后平均收縮壓為147mmHg,差異均顯著。

    主要終點(diǎn)指標(biāo)為14日或出院時(shí)死亡或重度殘疾率（改良Rankin量表評(píng)分≥3）。治療組與對(duì)照組達(dá)到該終點(diǎn)指標(biāo)的比例均為34%,14日或出院時(shí)平均改良Rankin量表評(píng)分均為2.

    何博士和Sila博士均聲稱無利益沖突披露。

    專家點(diǎn)評(píng)：降壓治療令人放心

    Sila博士評(píng)論指出，大多數(shù)急性缺血性腦卒中患者出現(xiàn)血壓升高，這可能對(duì)患者不利，也可能具有保護(hù)作用。這項(xiàng)最大規(guī)模的急性缺血性腦卒中降壓治療研究結(jié)果為我們對(duì)這類患者的臨床判斷提供了新的依據(jù)，即輕度卒中（平均NIH卒中量表評(píng)分為4）急性期過后、無大血管阻塞、血壓中度升高且未接受再灌注治療的患者。

    令人欣慰的是，研究結(jié)果顯示，卒中發(fā)作24小時(shí)后血壓平均降低12.7%雖未改善主要終點(diǎn)，但也未使結(jié)局惡化。這表明我們可以在降壓治療方面有所突破。在目前美國實(shí)踐中，部分醫(yī)生嘗試對(duì)血壓中度升高患者采取減壓治療。許多美國卒中病房已習(xí)慣于對(duì)組織型纖溶酶原激活劑治療患者應(yīng)用血壓監(jiān)測儀并控制血壓<180mmHg,這一方案也常用于未接受溶栓治療的缺血性卒中患者。

    Sila博士認(rèn)為，對(duì)于這項(xiàng)研究的受試者來說，這種更加積極的降壓措施或許是一種安全的選擇。

    By: MITCHEL L. ZOLER, Clinical Neurology News Digital Network

    DALLAS – Immediate blood pressure reduction in hypertensive acute ischemic stroke patients did not reduce death and disability after 14 days, but the strategy was safe and did not worsen patient's 14-day outcomes, a randomized controlled study has shown.

    The findings suggest that, among patients with relatively mild acute ischemic strokes and a systolic blood pressure of 140-219 mm Hg, “the decision to lower blood pressure with antihypertensive treatment should be based on individual clinical judgment,” Dr. Jiang He said at the American Heart Association scientific sessions.

    Elevated blood pressure immediately following an ischemic stroke poses a risk of hemorrhagic conversion or cerebral edema, but an elevated blood pressure also might be protective by forcing more blood into the penumbra around the stroke site. Blood pressure reduction measures are not appropriate for patients treated by reperfusion, but they are considered necessary for patients with “markedly elevated” blood pressure, generally defined as a systolic pressure of 220 mm Hg or higher, he said.

    U.S. guidelines on stroke management published earlier this year noted that the data to guide recommendations for treating less severe arterial hypertension, in the range studied in this trial, are “inconclusive or conflicting,” and that “the benefit of treating arterial hypertension in the setting of acute ischemic stroke is not well established” （Stroke 2013;44:870-947）。 Some U.S. clinicians, however, take steps to reduce moderately elevated blood pressure in acute ischemic stroke patients, especially when systolic pressures are at or close to 200 mm Hg.

    Based on the new findings, Dr. Sila proposed in her formal comments a strategy for managing patients with mild ischemic strokes who do not undergo reperfusion treatment and have a systolic pressure of 140-219 mm Hg more than 15 hours after their stroke onset and no major-vessel stenosis or occlusion. She suggested that a “reasonable” goal was to lower blood pressure by 10%-15% over the first 24 hours of treatment, with a goal blood pressure of less than 140/90 mm Hg within the next 7 days.

    The China Antihypertensive Trial in Acute Ischemic Stroke （CATIS） randomized 4,071 patients aged 22 years or older with a confirmed ischemic stroke who did not undergo reperfusion treatment at 26 hospitals in China. Their average age was 62 years, they were seen an average of 15 hours after their stroke onset, and they had a median National Institutes of Health Stroke Scale score of 4.

    The 2,038 patients randomized to blood pressure reduction received an intravenous angiotensin-converting enzyme inhibitor, enalapril, as their first-line treatment, followed by a calcium channel blocker as second-line treatment and a diuretic as a third-line agent. The objective was to reduce systolic pressure by 10%-25% within the first 24 hours, with a goal blood pressure of less than 140/90 mm Hg after 7 days.

    The treatments were effective, resulting in an average 13% reduction in blood pressure in treated patients after 24 hours （an average drop of 22 mm Hg）， and an average systolic pressure of 137 mm Hg after 7 days. The control patients had an average 7% reduction in their systolic pressure, an average reduction of 13 mm Hg after 24 hours, and an average systolic pressure of 147 mm Hg after 7 days. All of the differences were significant.

    The study's primary endpoint was the rate of death or major disability （a modified Rankin score of 3 or higher） at 14 days or at the time of hospital discharge. This endpoint occurred in 34% of patients in both the intervention and control arms, reported Dr. He, professor of epidemiology at Tulane University in New Orleans. After 14 days or at discharge, the average modified Rankin score was 2 for patients in both treatment arms.

    The report by Dr. He and his associates was published online in JAMA （2013 Nov. 17 [doi:10.1001/jama.2013.282543]） concurrently with his presentation.

    Dr. He and Dr. Sila said that they had no disclosures.

    View on the News

    Reassurance on blood pressure lowering

    Elevated blood pressure occurs in most patients with acute ischemic stroke, and it may be harmful but might also be protective. The results of this study, the largest reported trial of blood pressure management in acute ischemic stroke patients, add something to our clinical judgment for the subset of patients who match those enrolled in the study: patients beyond the hyper-acute phase with a mild stroke （average NIH Stroke Scale score of 4）， no major-vessel occlusions, moderately elevated blood pressure, and no reperfusion treatment.

    In this trial, an average blood pressure reduction of 12.7% after 24 hours did not improve the primary endpoint but it did not worsen recovery. That is reassuring. It shows that we can push the envelope a little in our use of blood pressure reduction. In current U.S. practice, some clinicians will try to reduce blood pressure in patients with moderately elevated pressure. Many U.S. stroke units are comfortable with blood pressure monitoring and with the target of less than 180 mm Hg used for patients treated with tissue plasminogen activator. These protocols are often also applied to ischemic stroke patients not treated with fibrinolysis because it is part of their usual practice.

    My take on the findings is that, for the types of patients enrolled in this study, this strategy of more active blood pressure management to get pressure down to a goal level could be a safe option.

    Dr. Cathy Sila is professor of neurology and director of the stroke and cerebrovascular center at Case Medical Center in Cleveland. She made these comments as the designated discussant for the report and in an interview.