A Phase 3 interventional study of Aspirin and Vitamin E in Cardiovascular Diseases, Cerebrovascular Disorders and Coronary Disease, sponsored by Brigham and Women's Hospital. Completed. Open to female participants aged 45 Years and older. Per ClinicalTrials.gov, last updated 2012-06-15.
Sponsored by Brigham and Women's Hospital · Phase 3, Interventional, and Prevention
The purpose of this study is to evaluate the effects of low-dose aspirin and vitamin E in primary prevention of cardiovascular disease and cancer in apparently healthy women.
BACKGROUND:
Various doses of aspirin have been shown to be effective in preventing thrombosis or vascular occlusion in several clinical conditions. Short-term studies have documented the efficacy of aspirin in preventing occlusion of saphenous vein bypass grants, preventing myocardial infarction in patients with unstable angina, preventing transient ischemic attacks and stroke in men with cerebral vascular disease, preventing occlusion of injured coronary arteries following transluminal angioplasty and aiding in reducing myocardial infarction and total mortality in patients receiving fibrinolytic therapy. Additionally, aspirin has been effective in the secondary prevention of myocardial infarction in subjects with known coronary artery disease. The results of the Physicians' Health Study, a large-scale primary prevention trial of aspirin in male physicians, have shown a decrease in myocardial infarction, a non-significant increase in cerebral vascular events, and no difference in overall mortality. However, few studies have addressed the efficacy of aspirin in vascular diseases in women, and it is possible that the risk to benefit ratio may be different in women. Specifically, there have been no large primary prevention trials in women, who are at risk of coronary heart disease, especially after menopause.
DESIGN NARRATIVE:
The Women's Health Study (WHS) is a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design. The WHS is sponsored by both NHBLI (HL080467) and NCI (CA047988). Approximately 1.75 million female health professionals were contacted by mail to determine if they were suitable for inclusion in the study. A three-month run-in phase was performed to screen out those with poor compliance. Randomization, which began in February 1993 and ended in January 1996, was stratified on five-year age groups. A total of 39,876 participants were randomly assigned to either Vitamin E (600 IU every other day) or placebo; and to aspirin (100 mg every other day) or placebo. IN the 2x2 factorial design, women were randomly assigned to active aspirin and placebo vitamin E (n=9,968), placebo aspirin and active vitamin E (n=9,971), active aspirin and active vitamin E (n=9,966), or placebo aspirin and placebo vitamin E (n=9,971). A description of the characteristics of women in these 4 groups is provided in J Women's Health Gend Based Med 2000;9:19-27. In the main analyses, all women on active aspirin (n=19,934) were compared to women on placebo aspirin (n=19,942); and all women on active vitamin E (n=19,937) were compared to women on placebo aspirin (n=19,939).
As part of the initial trial, pre-randomization blood samples from 28,345 participants were frozen and stored for genetic analysis which has been supported by non-federal sources.
The primary endpoint is the reduction of the risk of all important vascular events (a combined endpoint of nonfatal myocardial infarction, nonfatal stroke, and total cardiovascular death) and a decrease in the incidence of total malignant neoplasms of epithelial cell origin. Secondary endpoints are the individual components of the combined endpoints. Compliance is measured by replies to a questionnaire sent out every year. The trial was completed in 2004 and results were published in 2005 (N Engl J Med 2005;352:1293-304; JAMA 2005;294:47-55; JAMA 2005;294:56-65).
Currently, women are being followed on an observational basis.
374 studies on the registry are indexed under Cerebrovascular Disorders; 129 are open to participants now.
This study's enrollment of 39,876 is above the median of 110 across 214 interventional studies indexed under Cerebrovascular Disorders.
Browse Cerebrovascular Disorders studies →Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.
Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Vitamin E (600 IU every other day) and aspirin (100 mg every other day)
Drug: Aspirin · Drug: Vitamin E
Vitamin E (600 IU every other day) and placebo
Drug: Vitamin E · Behavioral: Placebo
Aspirin (100 mg every other day) and placebo
Drug: Aspirin · Behavioral: Placebo
Placebo and placebo
Behavioral: Placebo
Participants will receive 100 mg of aspirin every other day.
Participants will receive 600 IU of vitamin E every other day.
Participants will receive placebo.
Number of Participants With Major Cardiovascular Events (a Combined Endpoint of Nonfatal Myocardial Infarction, Nonfatal Stroke, and Total Cardiovascular Death)
Time frame: Average follow-up 10.1 years
Number of Participants With Cancer, Excluding Nonmelanoma Skin Cancer
Time frame: Average follow-up 10.1 years
| Milestone | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos |
|---|---|---|---|---|
| Started | 9968 | 9971 | 9966 | 9971 |
| Completed | 9968 | 9971 | 9966 | 9971 |
| Not completed | 0 | 0 | 0 | 0 |
| Participants | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos |
|---|---|---|---|---|
| Major cardiovascular event | 245 (0.80 to 1.03) | 250 (0.82 to 1.05) | 232 | 272 |
| Stroke | 113 (0.69 to 0.99) | 133 (0.82 to 1.17) | 108 | 133 |
| Myocardial infarction | 96 (0.84 to 1.25) | 94 (0.82 to 1.23) | 102 | 99 |
| Cardiovascular death | 66 (0.74 to 1.22) | 52 (0.59 to 0.98) | 54 | 74 |
| participants | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos |
|---|---|---|---|---|
| Total invasive cancer | 722 (0.94 to 1.08) | 721 (0.94 to 1.08) | 716 | 706 |
| Cancer death | 132 (0.81 to 1.11) | 156 (0.95 to 1.32) | 152 | 143 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Aspirin Only | — | 27/9,968 (0.3%) | 5,969/9,968 (59.9%) |
| Vitamin E Only | — | 20/9,971 (0.2%) | 5,915/9,971 (59.3%) |
| Aspirin + Vitamin E | — | 24/9,966 (0.2%) | 5,887/9,966 (59.1%) |
| Both Placebos | — | 21/9,971 (0.2%) | 6,000/9,971 (60.2%) |
| Event | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos |
|---|---|---|---|---|
| hemorrhagic strokeBlood and lymphatic system disorders | 27/9968 | 20/9971 | 24/9966 | 21/9971 |
| Event | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos |
|---|---|---|---|---|
| report of GI upsetGastrointestinal disorders | 5969/9968 | 5915/9971 | 5887/9966 | 6000/9971 |
| easy bruisingBlood and lymphatic system disorders | 5297/9968 | 4247/9971 | 5263/9966 | 4247/9971 |
| epistaxisBlood and lymphatic system disorders | 1854/9968 | 1703/9971 | 1947/9966 | 1618/9971 |
| hematuriaBlood and lymphatic system disorders | 1534/9968 | 1467/9971 | 1505/9966 | 1411/9971 |
| Age, Categorical(Participants) | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 8981 | 8974 | 8969 | 8984 | 35908 |
| >=65 years | 987 | 997 | 997 | 987 | 3968 |
| Age, Continuous(years) | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos | Total |
|---|---|---|---|---|---|
| Mean | 53.9 ± 7.1 | 53.9 ± 7.1 | 53.9 ± 7.1 | 53.9 ± 7.1 | 53.9 ± 7.1 |
| Sex: Female, Male(Participants) | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos | Total |
|---|---|---|---|---|---|
| Female | 9968 | 9971 | 9966 | 9971 | 39876 |
| Male | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Aspirin Only | Vitamin E Only | Aspirin + Vitamin E | Both Placebos | Total |
|---|---|---|---|---|---|
| United States | 9968 | 9971 | 9966 | 9971 | 39876 |
No study locations are listed for this record.
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