Glynn R J, Buring J E, Manson J E, LaMotte F, Hennekens C H
Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
Arch Intern Med. 1994;154(23):2649-57. doi: 10.1001/archinte.1994.00420230032005.
The primary aim of this article was to explore, in subgroup analyses, whether participants with differing frequencies of aspirin consumption in a randomized, double-blind, placebo-controlled, primary prevention trial had different magnitudes of benefit in the prevention of myocardial infarction. Secondary aims were to identify factors associated with adherence and to examine the relationship of adherence with cardiovascular outcomes in the placebo group.
The Physicians' Health Study randomized 22071 US male physicians who were free of myocardial infarction and cerebrovascular disease at baseline. The average follow-up during the aspirin component of the trial was 60.2 months. Baseline cardiovascular risk factors and adherence to therapy during the trial were assessed by questionnaire; cardiovascular outcomes were reported by questionnaire and confirmed by record review by an Endpoints Committee.
Several cardiovascular disease risk factors assessed at baseline were related to poor adherence (taking < 50% of study tablets): cigarette smoking, obesity, lack of exercise, and history of angina. After adjusting for baseline differences in risk factors, participants in the aspirin group with excellent adherence (taking at least 95% of study tablets) had a statistically significant 51% reduction in myocardial infarction compared with those with excellent adherence in the placebo group. Those in the aspirin group with poor adherence had a smaller, non-significant reduction in risk of myocardial infarction (a 17% reduction associated with taking < 50% of study tablets). In the placebo group better adherence was not associated with decreased risk of myocardial infarction, but was strongly associated with decreased risk of death.
These subgroup data raise the possibility that a less than alternate day aspirin regimen may yield lower benefits in the prevention of myocardial infarction. Alternate explanations are that these analyses reflect either the play of chance or effects of uncontrolled confounding since comparisons were no longer randomized. Randomized trials are necessary to address the question of frequency of administration of aspirin to achieve optimal benefits in primary prevention of myocardial infarction.
本文的主要目的是在亚组分析中探讨，在一项随机、双盲、安慰剂对照的一级预防试验中，服用阿司匹林频率不同的参与者在预防心肌梗死方面是否有不同程度的获益。次要目的是确定与依从性相关的因素，并研究安慰剂组中依从性与心血管结局之间的关系。
医师健康研究对22071名基线时无心肌梗死和脑血管疾病的美国男性医师进行了随机分组。试验中阿司匹林部分的平均随访时间为60.2个月。通过问卷调查评估基线心血管危险因素和试验期间的治疗依从性；心血管结局通过问卷调查报告，并由终点委员会进行记录审查确认。
在基线时评估的几个心血管疾病危险因素与依从性差（服用少于50%的研究药片）有关：吸烟、肥胖、缺乏运动和心绞痛病史。在调整了危险因素的基线差异后，阿司匹林组中依从性极佳（服用至少95%的研究药片）的参与者与安慰剂组中依从性极佳的参与者相比，心肌梗死发生率有统计学意义的降低，降低了51%。阿司匹林组中依从性差的参与者心肌梗死风险降低幅度较小，无统计学意义（服用少于50%的研究药片导致风险降低17%）。在安慰剂组中，更好的依从性与心肌梗死风险降低无关，但与死亡风险降低密切相关。
这些亚组数据提出了一种可能性，即少于隔日服用阿司匹林的方案在预防心肌梗死方面可能获益较低。其他解释是，这些分析要么反映了偶然性，要么反映了未控制的混杂因素的影响，因为比较不再是随机的。需要进行随机试验来解决阿司匹林给药频率的问题，以在心肌梗死一级预防中实现最佳获益。
