January 19, 2007 — 一篇新的报告中，研究者开始老年人初次
中风预防试验的原理阐述和初步研究设计，特别是在血压控制良好的情况下，比较statin治疗和安慰剂的结果。
作者指出，在那些心血管疾病或
糖尿病的
临床研究中，Statins 相当程度地降低心血管事件的风险，但是目前关于70岁以上病患该如何使用statins和是否该使用statins，和这些七、八十岁但没有CVD或糖尿病者最好控制血压是多少的资料很少—在注重健康的婴儿潮世代中，这一族群的人数已经渐增。
第一作者、爱荷华大学的Jennifer G. Robinson医师向Medscape表示，目前为止，我们所作的试验考量错过了疾病的大量发生，因为大多数的研究排除了这些老年者，大家都知道这是重要的，却难以对老年人进行研究，因为可能有无法接受的死亡率，但我们不能因为不容易招募研究对象而卸责。
他们的报告包括回顾现有的证据和提出一个新的试验计划，此报告登载于2006年12月28日的线上版中风期刊。
【PROSPER试验后仍有疑问】
Robinson医师指出，身为一个脂质学家，如何研究70岁以上者的脂质与血压控制的问题是她时常听到的，特别是从那些一般开业医师。她说，本篇文章所用的资料主要来源是“Pravastatin 用于有血管疾病风险的老年人之前溯式研究(Prospective Study of Pravastatin in the Elderly at Risk of Vascular Disease/ PROSPER)试验”的结果(Shepherd J 等人. Lancet. 2002;360:1623-1630)，显示statins用于70到82岁之间有心血管疾病或中风或者是高风险病患的好处，但是该研究中有一些可讨论之处。
Robinson医师指出，虽然以statin治疗有好处，仍受制于死亡和非致命MI，且对此族群无中风预防效果；对此试验所关注的是，血压并未控制良好之事实。
她表示，目前的报告中，我们回顾证据，研究证据间的差异与各自的基础，粗略地概述我们将如何描述此一问题，她指出，将提出一个安慰剂控制的statin试验，因为我们真正需要证实以statins治疗老年人是有效且安全的。
有更多的证据支持这一群病患的血压降低可以减少心血管和肾脏疾病，不过有关老年人的适切治疗目标目前并不清楚。
他们具体地提议一个五年的2 x 2阶乘设计的研究，纳入至少5000 位70岁以上的病患，这些人试验开始时没有心血管疾病、糖尿病或者其他会造成存活不到五年的病症，病患被随机分派接受statin或者安慰剂，治疗选择和剂量是依据已知70岁以上的LDL治疗目标(小于100 mg/dL)的安全纪录。
这些受试者接着再度随机接受两种抗
高血压处方之一，以达到收缩压小于140 mm Hg，若是那些脉压（收缩压－舒张压）增大者，例如超过80者，如果病患耐受良好，治疗目标是收缩压小于140 mm Hg，所有参与者目标是收缩压小于160 mm Hg；他们指出，治疗处方的选择是依照最近的资料，对某些病患，必要时需以多种药物治疗。
本篇的共同作者包括许多不同学科的专家，包括高血压专家，芝加哥大学的George Bakris医师、脂质专家，西北大学的Neil Stone医师、爱荷华大学的中风流行病学专家James Torner博士，以及老年专家Robert Wallace医师；Robinson医师表示，我们真的尝试要达成这个跨领域研究计划。
她指出，基于这主要目标，将检视研究族群的一些其他问题，如对失智症、心脏衰竭、肾脏功能和整体功能的治疗效果。
该团队已经计划和国家健康研究中心讨论这样的一个试验的可行性，而且有数个药厂表达赞助支持此试验的意愿；Robinson医师表示，为了让计划开始执行，已经运作多年，我想，即将可以正式开始。
【一个平衡状态】
在一篇编辑评论中，也曾做过初步中风预防研究的芝加哥中风研究中心的Philip B. Gorelick医师表示，Robinson医师和同事所提议的这个心血管初步预防试验，将提出有关老年人使用statin治疗以良好控制血压的安全性与好处的重要答案。
Gorelick医师向Medscape表示，对这样一个试验的临床争论是强烈的，我们不知道该做什么，举例来说，血压降低的目标为何；他指出，老年人开始有一些认知缺损，虽然降低血压看似可以预防心智缺损发生，但可能对已经接受脑部血流灌注的病患不利。
Gorelick医师表示，所以我大力支持这个研究，我面对许多年长者，我想这个研究将可回答一些重要问题。
他表示他充满热忱且接受Robinson医师的邀请参加试验，他期待和爱荷华的团队和其他许多研究人员合作。
Robinson医师接受国家健康研究中心、Abbott、Andrx Labs、AstraZeneca、Atherogenics、Bristol-Myers Squibb、GlaxoSmithKline、Hoffman La Roche、Merck、Pfizer、Procter & Gamble、Schering-Plough、Sankyo、Takeda和Wyeth Ayerst的基金；接受Merck 和Pfizer教育计划的发言费；Merck、Pfizer、Proliant和Wellmark担任谘询建议委员；其他作者，Gorelick 医师在过去的12个月担任Boehringer Ingelheim、Pfizer以及医学教育发展中心的谘询顾问，接受Boehringer Ingelheim 的发言费。
Stroke. 2007: 发表于December 28, 2006.
Time for a Primary Stroke Prevention Trial in the Elderly?
By Susan Jeffrey
Medscape Medical News
January 19, 2007 ??In a new report, researchers set out their rationale and a preliminary design for a trial of primary stroke prevention in the elderly, specifically comparing statin therapy with placebo against a background of good blood pressure control.
Statins certainly reduce the risk of cardiovascular events in those with clinical cardiovascular disease or diabetes, the authors note, but few data are currently available on how or whether to use statins in patients over 70 years old and what the best blood pressure targets are for those who have reached their 70s or 80s without either CVD or diabetes ??a growing group among health-conscious baby boomers.
"We've missed the vast burden of disease in the trials that have been done to date," first author Jennifer G. Robinson, MD, from the University of Iowa, in Iowa City, told Medscape, as most studies excluded these older age groups. "People say, Yes, it's important, but it's so hard to do a study in the elderly where there's competing mortality.?.?.?.?But it doesn't get you off the hook because it's hard to recruit for them."
Their report, which includes a review of the available evidence and a proposed design for the new trial, appears online December 28, 2006 in Stroke.
Questions Remain After PROSPER
Dr. Robinson points out that as a lipidologist, this question of how to approach lipid and blood pressure management in those older than 70 years is typical of what she often hears, particularly from physicians in general practice. The main source of data to address this issue come from results of the Prospective Study of Pravastatin in the Elderly at Risk of Vascular Disease (PROSPER) trial (Shepherd J et al. Lancet. 2002;360:1623-1630), which did show a benefit with statins in patients between 70 and 82 years of age with or at a high risk of developing cardiovascular disease or stroke, but there were issues with that study, she says.
Although there was a benefit seen with statin treatment, it was confined to death and nonfatal MI, and no effect was seen for stroke prevention in this population. Of concern with the trial was the fact that blood pressure did not appear to be adequately controlled, Dr. Robinson noted.
In the current paper, she said, "We reviewed the evidence, looking at where the gaps in the evidence were, and on the basis of that, roughly outlined how we thought this question would be addressed." They propose a placebo-controlled statin trial because, she noted, "We really need to prove that treating older people with statins is beneficial and safe."
There is more evidence to support blood pressure reduction in this group to reduce both cardiovascular and renal events, although the optimal target for elderly individuals is not clear at this point.
Specifically, they advocate a 5-year study with a 2 x 2 factorial design, enrolling at least 5000 patients older than 70 years who are free at baseline of cardiovascular disease, diabetes, or comorbidities likely to limit their survival to less than 5 years. Patients would be randomized to receive a statin or placebo. "Treatment choice and dose would depend on an established record of safety in those older than 70 years as well as the LDL treatment target (less than 100 mg/dL)."
Subjects would then be rerandomized to 1 of 2 antihypertensive regimens to achieve a systolic blood pressure of less than 140 mm Hg, "or, in those with wide pulse pressure, ie, greater than 80, to try to achieve a level of less than 140 mm Hg if tolerated by the patient, with the goal of a systolic blood pressure of less than 160 mm Hg in all participants." The choice of treatment regimen would depend on the most recent data, they note, and multiple agents would be needed for a significant number of participants.
Coauthors on the paper include specialists from a number of disciplines, including hypertension expert George Bakris, MD, from the University of Chicago, in Illinois, and lipidologist Neil Stone, MD, from Northwestern University, in Evanston, Illinois. James Torner, PhD, a stroke epidemiologist, and Robert Wallace, MD, an expert on aging, are both from the University of Iowa, Iowa City. "We're really trying to make this a cross-cutting proposal," Dr. Robinson said.
Along with this primary focus, the study population would allow examination of a number of other questions, such as the effects of treatment on dementia, heart failure, kidney function, and overall functionality, she noted.
The group is already planning to meet with the National Institutes of Health to discuss the feasibility of such a trial, and several pharmaceutical sponsors have expressed interest in supporting it, Dr. Robinson said. "It takes a few years to get the ball rolling, but I think it's a trial that's going to happen."
A State of Equipoise
In an editorial accompanying the paper, Philip B. Gorelick, MD, from the Center for Stroke Research in Chicago, Illinois, who has made primary stroke prevention the focus of some of his own research, writes that a cardiovascular primary-prevention trial such as that proposed by Dr. Robinson and colleagues "holds promise to provide important answers in relation to the safety and benefit of statin therapy in the elderly and the proper blood pressure?owering regimen and blood pressure target."
"The clinical argument is strong" for such a trial, Dr. Gorelick told Medscape. "We don't know what to do, for example, in terms of the target for blood pressure lowering." Elderly patients begin to have some cognitive impairment, he pointed out, and although it seems clear that lowering blood pressure prevents cognitive impairment before it begins, it may be detrimental to those who already have some challenge to brain perfusion.
"So I'm a big supporter of this," Dr. Gorelick said. "I deal a lot with the elderly, and I think this study is going to answer a lot of important questions."
He is sufficiently enthusiastic that he has accepted an invitation from Dr. Robinson to participate in the trial, he added. "I'm looking forward to working with the Iowa group as well as many investigators around the country in getting this off the ground."
Dr. Robinson discloses that she has received grants from the National Institutes of Health, Abbott, Andrx Labs, AstraZeneca, Atherogenics, Bristol-Myers Squibb, GlaxoSmithKline, Hoffman La Roche, Merck, Pfizer, Procter & Gamble, Schering-Plough, Sankyo, Takeda, and Wyeth Ayerst; having received speaker honoraria for educational programs from Merck and Pfizer; and having served on consultant/advisory boards for Merck, Pfizer, Proliant, and Wellmark. Disclosures for coauthors appear in the paper. Dr. Gorelick discloses that in the past 12 months he has been a consultant to Boehringer Ingelheim, Pfizer, and the Discovery Institute of Medical Education and has received honoraria for serving on a speaker's bureau for Boehringer Ingelheim.
Stroke. 2007: Published December 28, 2006.
作者：
Susan Jeffrey 2007-6-20