Causal Models for CVD Use by Aspirin and Vitamin E in the Women's Health Study

女性健康研究中阿司匹林和维生素 E 使用导致 CVD 的因果模型

• 批准号: 7364187
• 负责人: Nancy R Cook
• 金额: $ 12.6万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7364187
• 关键词: Address; Adult; Advisory Committees; Age; Arts; Aspirin; Cardiovascular Diseases; Cardiovascular Models; Cardiovascular system; Cessation of life; Chemoprevention; Coronary heart disease; Data; Databases; Development; Dose; Elderly; End Point; Event; Frequencies; Future; Gender; Guidelines; Health; Hypertension; Individual; Intervention; Menopausal Status; Meta-Analysis; Methods; Modeling; Modification; Myocardial Infarction; Outcome; Participant; Physicians; Postmenopause; Preventive; Primary Prevention; Public Health; Publishing; Questionnaires; Randomized; Randomized Controlled Clinical Trials; Recommendation; Reporting; Research Personnel; Risk; Services; Smoking; Source; Statistical Methods; Stroke; Subgroup; Time; Update; Vitamin E; Woman; Women' s Health; age effect; cardiovascular disorder risk; cardiovascular risk factor; cooking; day; experience; hormone therapy; men; mortality; programs; protective effect

DESCRIPTION (provided by applicant): Recent randomized trial data from the Women's Health Study (WHS) demonstrated no overall effect of low dose aspirin on the primary endpoint of major cardiovascular disease (CVD), including MI, stroke, and CVD death. This contrasts with a meta-analysis of previous trials, mostly in men, that showed a 28% reduction in coronary heart disease. Whether the discrepancies are due to gender or dose remains unanswered. While additional trial data would be necessary to fully address this issue, WHS data can be used to determine whether varying usage within the study is a determinant of future CVD events. We propose to use state-of- the art statistical methods to estimate the causal effects of actual aspirin use during the trial to determine if actual use is more predictive of later CVD, and whether higher actual doses used have a greater impact on CVD. In addition, we will use the updated time-varying covariables to examine whether they modify the effect of actual aspirin use during the trial using similar methods. While data for the vitamin E intervention in the WHS are more consistent with previous null trial data, we found a reduction in the secondary endpoint of CVD mortality, as well as effect modification by age. There may be confounding by intermediate events in these data, however, which could distort estimates from both randomized as well as observational analyses. We will thus apply the same causal methods to determine whether there is an effect of actual vitamin E use or dose on the development of CVD after adjusting for time-varying covariables, as well as exploring the presence of modification of the effect of vitamin E. A 2002 recommendation by the Preventive Services Task Force for primary prevention strongly recommended that clinicians consider aspirin chemoprevention for all adults at increased risk of coronary heart disease, including postmenopausal women. The true effect of aspirin in women, and of varying effects by dose, thus has major public health relevance. For vitamin E, data from the WHS support current guidelines stating that use is not justified for CVD reduction. The findings of reduced risk of CVD mortality, however, as well as effects by age, should be explored further to clarify the public health message.

描述(由申请人提供)：最近来自妇女健康研究(WHS)的随机试验数据表明，小剂量阿司匹林对主要心血管疾病(CVD)的主要终点没有总体影响，包括心肌梗死、中风和CVD死亡。这与之前试验的荟萃分析形成了鲜明对比，该试验主要针对男性，结果显示冠心病的发病率降低了28%。这种差异是由性别还是剂量引起的，目前还没有答案。虽然需要更多的试验数据来充分解决这个问题，但WHS数据可以用来确定研究中不同的使用情况是否是未来心血管事件的决定因素。我们建议使用最先进的统计方法来估计试验期间实际使用阿司匹林的因果影响，以确定实际使用是否更能预测以后的心血管疾病，以及实际使用的较高剂量是否对心血管疾病有更大的影响。此外，我们将使用更新的时变协变量来检查它们是否会使用类似的方法在试验期间改变实际使用阿司匹林的效果。虽然WHS中维生素E干预的数据与之前的零试验数据更一致，但我们发现心血管疾病死亡率的次要终点减少了，并且影响了年龄的改变。然而，这些数据中可能存在中间事件的混淆，这可能会扭曲随机分析和观测分析的估计。因此，我们将应用相同的因果方法，在调整了随时间变化的协变量后，确定实际维生素E的使用或剂量是否对心血管疾病的发展有影响，并探索维生素E的影响是否存在修改。预防服务工作组2002年提出的一级预防建议强烈建议临床医生考虑对包括绝经后妇女在内的所有冠心病风险增加的成年人进行阿司匹林的化学预防。因此，阿司匹林对女性的真实影响以及不同剂量的影响具有重大的公共卫生意义。对于维生素E，来自WHS的数据支持当前的指南，该指南指出，使用维生素E不能减少心血管疾病。然而，降低心血管疾病死亡风险的研究结果以及年龄的影响应该进一步探讨，以澄清公共卫生信息。