降压治疗不能改善缺血性脑卒中患者生存

达拉斯——美国心脏协会(AHA)2013科学年会上报告的一项中国随机对照研究结果显示，立即采取降压治疗并不能降低高血压型急性缺血性脑卒中患者14天后的死亡率和残疾率，不过这一策略是安全的，不会使患者结局恶化。该研究结果同时在线发表在《美国医学会杂志》上(2013 Nov. 17[doi:10.1001/jama.2013.282543])。

美国杜兰大学流行病学教授何江博士报告称，中国急性缺血性脑卒中降压试验(CATIS)结果表明，对于收缩压介于140~219 mmHg的相对轻度缺血性脑卒中患者，是否采取降压治疗应因人而异。

研究者认为，缺血性脑卒中发作后随即出现的血压升高是出血转化或脑水肿的风险因素，但也可能促使更多的血液进入卒中部位周围半影区从而起到保护作用。降压措施不适合于再灌注治疗患者，但对于血压明显升高(通常定义为收缩压≥220 mmHg)的患者则被认为是必须的。

今年早些时候公布的美国卒中诊治指南指出，对于不太严重动脉高血压(严重程度在这项试验范围之内)采取降压治疗的推荐依据存在争议，动脉高血压治疗对急性缺血性脑卒中患者的受益尚不十分确定(Stroke 2013;44:870-947)。但部分美国医生对缺血性脑卒中患者采取适度降压措施，特别是对于收缩压达到或接近200 mmHg的患者。

基于这项新的研究结果，克利夫兰Case医学中心卒中与脑血管中心主任、神经学教授Cathy Sila博士提出了一项针对未接受再灌注治疗、卒中15小时后收缩压为140~219 mmHg且无大血管狭窄或阻塞的轻度缺血性脑卒中患者的治疗策略。她建议，合理的目标是在治疗最初24小时内血压降低10~15%，此后7日内目标血压<140/90 mmHg。

CATIS纳入了中国26家医院的4,071例年龄≥22岁、未接受再灌注治疗的缺血性脑卒中确诊患者。平均年龄62岁，平均就诊时间为卒中发作后15小时，中位NIH卒中量表评分为4。

2,038例患者随机接受降压治疗，静注血管紧张素转化酶抑制剂依那普利作为一线治疗，钙离子通道阻滞剂和利尿剂分别作为二线和三线治疗。目标为最初24小时内收缩压下降10~25%，7日后血压<140/90 mm Hg。

降压治疗效果明显，治疗组24小时血压平均下降13%(平均降幅22 mmHg)，7日后平均收缩压为137 mmHg，而对照组24小时血压平均下降7%(平均降幅13 mmHg)，7日后平均收缩压为147 mmHg，差异均显著。

主要终点指标为14日或出院时死亡或重度残疾率(改良Rankin量表评分≥3)。治疗组与对照组达到该终点指标的比例均为34%，14日或出院时平均改良Rankin量表评分均为2。

何博士和Sila博士均声称无利益冲突披露。

专家点评：降压治疗令人放心

Sila博士评论指出，大多数急性缺血性脑卒中患者出现血压升高，这可能对患者不利，也可能具有保护作用。这项最大规模的急性缺血性脑卒中降压治疗研究结果为我们对这类患者的临床判断提供了新的依据，即轻度卒中(平均NIH卒中量表评分为4) 急性期过后、无大血管阻塞、血压中度升高且未接受再灌注治疗的患者。

令人欣慰的是，研究结果显示，卒中发作24小时后血压平均降低12.7%虽未改善主要终点，但也未使结局恶化。这表明我们可以在降压治疗方面有所突破。在目前美国实践中，部分医生尝试对血压中度升高患者采取减压治疗。许多美国卒中病房已习惯于对组织型纤溶酶原激活剂治疗患者应用血压监测仪并控制血压<180 mmHg，这一方案也常用于未接受溶栓治疗的缺血性卒中患者。

Sila博士认为，对于这项研究的受试者来说，这种更加积极的降压措施或许是一种安全的选择。


Cathy Sila博士

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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.

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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.