Prophylactic aspirin therapy did not reduce vascular events in a study of people who had a low ankle-brachial index but no clinical evidence of cardiovascular disease, according to a report in the March 3 issue of JAMA.

“This trial is the first to report on the effectiveness of aspirin in reducing major cardiovascular and cerebrovascular events in individuals from the general population who were free of clinical cardiovascular disease but at higher risk as identified by ABI screening,” said Dr. F. Gerald R. Fowkes of the University of Edinburgh and his associates in the Aspirin for Asymptomatic Atherosclerosis trial.

The randomized, double-blind trial involved 3,350 men and women aged 50-75 years when they were screened for a low (0.95 or lower) ankle-brachial index in 1998-2001. The subjects, all residents of central Scotland, had no clinical evidence of cardiovascular disease, but their low ABI put them at risk for coronary and cerebrovascular disease.

The study subjects were randomly assigned to receive 100 mg of enteric-coated aspirin or a placebo daily. They were followed at regular intervals for a mean of 8 years.

The primary end point – a composite of fatal or nonfatal coronary event, stroke, or revascularization procedure – was not statistically lower in subjects who took prophylactic aspirin (13.7 events per 1,000 person-years) than in those who took placebo (13.3 events per 1,000 person-years).

The secondary end point, which was angina, intermittent claudication, or transient ischemic attack in addition to the primary end point component, also did not differ between the intervention group (22.8 events per 1,000 person-years) and the placebo group (22.9 events per 1,000 person-years).

In addition, the two study groups did not differ significantly when each individual component of these composites was analyzed separately. And there was no significant difference in all-cause mortality between the aspirin group (12.8 deaths per 1,000 person-years) and the placebo group (13.5 deaths per 1,000 person-years).

However, aspirin therapy did confer a greater risk of harm than did placebo. “Although numbers were small, the trial results suggested an increased incidence of major hemorrhage and gastrointestinal ulcer, although not severe anemia, in the aspirin group, and more participants in the aspirin group than in the placebo group had fatal intracranial adverse events,” Dr. Fowkes and his colleagues wrote (JAMA 2010;303:841-8).

They noted that given the hazard ratios and confidence intervals in the data, the study could not rule out the possibility that aspirin prophylaxis might reduce cardiovascular risk by a small degree (16%) in healthy people found to have a low ABI. “However, extrapolating from the [nearly 29,000 people] screened for participation in our trial, a risk reduction of this order means that between 500 and 600 people from the general population would need to be screened and prescribed aspirin to prevent a single major cardiovascular event over an 8-year period.

“It is highly questionable whether the additional resources required to screen and treat such a large number of people to prevent only a small number of events would be justified, or indeed whether a larger trial to try [to] demonstrate such a small effect should be considered,” they added.

The study was funded by the British Heart Foundation and Chief Scientist’s Office, Scotland. Bayer HealthCare provided the aspirin and placebo tablets as well as funds for packaging and dispensing the drugs and conducting some statistical analysis. Dr. Fowkes reported financial ties to Bayer HealthCare, Sanofi-Aventis, and Bristol-Myers Squibb. Two associates also reported ties to Bayer HealthCare.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

根据3月3日发表于《美国医学会杂志》(JAMA)上的一项报告，在踝臂指数(ABI)低但无心血管疾病临床表现的个体中，阿司匹林预防治疗不能减少心血管事件。

 

爱丁堡大学的F. Gerald R. Fowkes博士及其同事在阿司匹林治疗无症状性动脉粥样硬化试验中说：“这项试验纳入来自一般人群的无临床心血管疾病但经ABI筛查认为风险较高的个体，首次对阿司匹林减少这类个体发生重大心血管和脑血管事件的有效性进行了评价。”

 

该随机双盲试验于1998~2001年期间通过筛查方式纳入3,350名踝臂指数低(≤0.95)的男性和女性受试者(年龄为50~75岁)。所有受试者均为苏格兰中部地区的居民。这些受试者无心血管疾病临床表现，但由于ABI低而存在发生冠状动脉和脑血管疾病的风险。

 

受试者随机接受100 mg肠溶阿司匹林或安慰剂治疗(每日1次)。定期对受试者进行随访，平均随访时间为8年。

 

阿司匹林预防治疗组主要终点(包括由致死性或非致死性冠脉事件、卒中或血运重建术组成的复合终点)发生率低于安慰剂组，但差异无统计学意义(13.7例事件/1,000人•年 对13.3例事件/1,000人•年)。

 

干预组和安慰剂组之间的次要终点(除主要终点组分之外，还包括心绞痛、间歇性跛行和短暂性缺血发作)发生率也无差异(22.8例事件/1,000人•年对22.9例事件/1,000人•年)。

 

此外，对这些复合终点的各个组分进行单独分析时，也未发现组间显著差异。阿司匹林组和安慰剂组之间的全因病死率无显著差异(12.8例死亡/1,000人•年对13.5例死亡/1,000人•年)。

 

然而，阿司匹林治疗引起的损害风险大于安慰剂。Fowkes博士及其同事写道：“试验结果显示，阿司匹林组大出血和胃肠道溃疡发生率增加(而重度贫血发生率未增加)，并且阿司匹林组致死性颅内不良事件发生率多于安慰剂组，尽管数值较小”(JAMA 2010;303:841-8)。

 

他们指出，考虑到数据的危险比和可信区间，该研究不能排除以下可能性，即阿司匹林预防治疗可能使ABI低的健康个体的心血管风险小幅降低(降幅为16%)。“然而，从本试验筛查的近29,000名个体外推，这一数量级的风险降幅意味着，为了预防一件重大心血管事件的发生，需要从一般人群中筛查出500~600名个体，并应用阿司匹林治疗8年。”

 

他们补充说：“非常值得质疑的两点是：①仅为预防少量事件的发生，就需要通过额外的资源来筛查和治疗数量如此大的个体，是否有其合理性？②为了试图证实如此小的效应而进行大规模的试验，是否有必要？”

 

该研究获英国心脏基金会和苏格兰首席科学家办公室资助。拜耳医药保健公司除了提供阿司匹林和安慰剂片剂之外，还为药品的包装和分发及一些统计学分析工作的开展提供必要资金。Fowkes博士声明其与拜耳医药保健公司、赛诺菲-安万特公司和百时美施贵宝公司存在经济利益关系。另外两位研究者也声明与拜耳医药保健公司存在经济利益关系。

 

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