Women's Health Study (WHS): A Randomized Trial of Low-dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Julie E. Buring, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00000479
First received: October 27, 1999
Last updated: June 12, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Cardiovascular Diseases
Cerebrovascular Disorders
Coronary Disease
Heart Diseases
Myocardial Infarction
Myocardial Ischemia
Vascular Diseases
Drug: Aspirin
Drug: Vitamin E
Behavioral: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Women's Health Study of Low-dose Aspirin and Vitamin E in Apparently Healthy Women

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Number of Participants With Cancer, Excluding Nonmelanoma Skin Cancer [ Time Frame: Average follow-up 10.1 years ] [ Designated as safety issue: No ]

Enrollment: 39876
Study Start Date: September 1992
Study Completion Date: February 2005
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Vitamin E (600 IU every other day) and aspirin (100 mg every other day)
Drug: Aspirin
Participants will receive 100 mg of aspirin every other day.
Drug: Vitamin E
Participants will receive 600 IU of vitamin E every other day.
Experimental: 2
Vitamin E (600 IU every other day) and placebo
Drug: Vitamin E
Participants will receive 600 IU of vitamin E every other day.
Behavioral: Placebo
Participants will receive placebo.
Experimental: 3
Aspirin (100 mg every other day) and placebo
Drug: Aspirin
Participants will receive 100 mg of aspirin every other day.
Behavioral: Placebo
Participants will receive placebo.
Placebo Comparator: 4
Placebo and placebo
Behavioral: Placebo
Participants will receive placebo.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Healthy women
  • No previous history of cardiovascular disease or cancer
  • No contraindications to aspirin or vitamin E
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000479

Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Julie Buring Brigham and Women's Hospital
  More Information

Publications:
Bassuk SS, Ridker PM, Manson JE, Buring JE. Aspirin and cardiovascular disease prevention in women: new findings from the Women's Health Study. Women's Health, 1:9-10, 2005.
Buring JE, Hennekens CH for the Women's Health Study Research Group. The Women's Health Study: rationale and background. J Myocardial Ischemia, 4:30-40, 1992.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Julie E. Buring, Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00000479     History of Changes
Other Study ID Numbers: 69, R01HL043851, HL043851, CA047988
Study First Received: October 27, 1999
Results First Received: December 5, 2011
Last Updated: June 12, 2012
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Cerebrovascular Disorders
Myocardial Ischemia
Coronary Artery Disease
Coronary Disease
Heart Diseases
Infarction
Ischemia
Myocardial Infarction
Vascular Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Necrosis
Aspirin
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014