The WOMEN Study: What is the Optimal Method for Ischemia Evaluation in WomeN?

NCT ID: NCT00282711

Last Updated: 2012-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

824 participants

Study Classification

OBSERVATIONAL

Study Start Date

2004-06-30

Study Completion Date

2010-12-31

Brief Summary

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The purpose of this study is to compare two types of exercise stress testing to find the best method for detecting heart disease in women.

Detailed Description

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Coronary artery disease remains the leading cause of morbidity and mortality in women accounting for more than 250,000 deaths per year. While mortality rates have decreased significantly in men during the last several decades, there has been little change for women. Furthermore, despite the high prevalence of ischemic heart disease (IHD) in women, most clinical trials have focused on male cohorts, resulting in a lack of data for women. Their exclusion from clinical trials has been primarily due to the following: 1) child- bearing potential, 2) beyond the arbitrary age limits established for trials, 3) frequent concomitant or advanced disease, and 4) inhomogeneity within the study population.

Extrapolation of the published clinical trial data (predominately obtained in men) for women is controversial due to differences in epidemiology of heart disease in women. Treatment is often sought later in life and is usually accompanied by more advanced disease and co-morbidities, which therefore, impact survival. In addition, women more frequently have an absence of clinical symptoms or an atypical presentation, making the diagnosis of coronary artery disease (CAD) challenging. Furthermore, women may also have their first manifestation of CAD as sudden death or acute myocardial infarction. Therefore, there is a clear need for the early identification of IHD in women so that treatments may be employed prior to having an advanced state of disease and higher risk for unfavorable outcomes.

The optimal non-invasive test for evaluation of IHD in women is unknown. A number of different modalities have been employed including exercise ECG stress testing, 2-dimensional stress echocardiography, single photon emission computerized tomography (SPECT) myocardial perfusion imaging, and electron beam tomography. Additionally, the cohort of women for whom testing is performed is also ill defined.

The most recent AHA/ACC guidelines suggest that ECG stress testing should be the preferred approach. Supportive data for this recommendation are controversial, as many of the studies examining the diagnostic value of ECG stress testing were largely performed in small cohorts of women and are dated. These trials indicate that the diagnostic accuracy of stress testing is only fair (sensitivity=32-89%; specificity=41-68%). A recent meta-analysis in 3,874 women demonstrated modest sensitivity and specificity, 62% and 69% respectively, even after adjustment for referral bias (8). Published guidelines have also included a meta-analysis and confirmed a low level (sensitivity=33%) of detection of disease. Additionally, the high rate of false positives, as well as the inability to fully ascertain the extent of disease, therefore limits the potential value of ECG stress testing.

Even though exercise stress testing is supported by recent clinical guidelines, the addition of SPECT myocardial perfusion imaging has independent and incremental diagnostic and prognostic value. Improved diagnostic accuracy has also been noted with perfusion imaging and its ability to predict cardiac events in women is well established. Furthermore, recent data supports the cost-effectiveness of strategies that employ myocardial perfusion imaging in the assessment of women at risk for ICD.

The current AHA/ACC recommendations fail to take into account that women often have limited ability to complete maximal exercise, a problem that is likely due to their older age and more frequent co-morbidities as compared with men. This functional impairment may lead to a lack of ischemia provocation and/or indeterminate exercise testing results. Maximal predicted heart rate, oxygen consumption, and, more commonly, metabolic equivalents (METs) are measures to estimate physical work capacity. The Duke Activity Status Index (DASI) is a simple 12-item questionnaire that estimates peak oxygen consumption. The Duke Activity Status Index (DASI) questionnaire may identify patients who are likely to perform inadequate exercise, which amounts to nearly 40% of all women referred for exercise testing.

The optimal strategy for the evaluation of women with suspected ischemic heart disease is unknown and quite controversial. Several algorithms have been suggested for the evaluation of women with suspected CAD. A recent consensus paper from the American Society of Nuclear Cardiology suggested a strategy that employed perfusion imaging, but provided little evidence to support such a clinical strategy, such as with a prospective clinical trial. The focus of this investigation is to compare different strategies for the assessment of women at intermediate or high clinical risk for IHD and to do so on a prospective, randomized basis. This study is therefore focused on providing a high level of clinical evidence on which to base future recommendations and guidelines for the care of women with heart disease.

Conditions

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Coronary Artery Disease Heart Disease Coronary Arteriosclerosis Cardiovascular Disease Myocardial Ischemia

Keywords

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Diagnostic Techniques, Radioisotope Radionuclide Imaging Diagnostic Techniques, Cardiovascular Heart Function tests

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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1

Standard Exercise treadmill test

No interventions assigned to this group

2

Exercise treadmill testing with nuclear imaging

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

\- Women 60 years of age and older presenting for the evaluation of chest pain, or other anginal equivalent symptoms while at an intermediate-high pretest risk for IHD

Exclusion Criteria

* Women with known CAD
* Women scoring \<5 METs on the DASI
* Nursing or pregnant females
* Nuclear medicine study within the preceding 10 days
* Electrocardiographic abnormalities precluding interpretation of peak stress changes including: Left bundle branch block, electronic ventricular pacemaker, left ventricular hypertrophy, WPW, and resting ST-T wave changes. Additionally, patients currently on digoxin therapy
* Significant valvular heart disease (i.e. severe aortic stenosis or regurgitation, or severe mitral insufficiency)
* Hemodynamic instability (blood pressure \>210/110 ml/Hg or \<90/60 mm/Hg)
* Left ventricular systolic dysfunction with a left ventricular ejection fraction less than 30 %
* Unavailability for long-term follow-up
Minimum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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GE Healthcare

INDUSTRY

Sponsor Role collaborator

Hartford Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gary V. Heller, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hartford Hospital, Hartford, CT

Robert C. Hendel, M.D.

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center, Chicago, IL

Jennifer H. Mieres, M.D.

Role: PRINCIPAL_INVESTIGATOR

North SHore University Hospital, Long Island, NY

Leslie J. Shaw, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Atlanta Cardiovascular Research Institute, Atlanta, GA

Locations

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Southwest Heart

Tucson, Arizona, United States

Site Status

Cardiology Consultants of Orange Country Medical Group, Inc

Anaheim, California, United States

Site Status

Escondido Cardiology Associates

Escondido, California, United States

Site Status

Mission Internal Medical Group

Mission Viejo, California, United States

Site Status

St. Joseph's Hospital Women's Hrt Cnt

Orange, California, United States

Site Status

Sutter Roseville Medical Center

Roseville, California, United States

Site Status

Sacramento Heart & Vascular Res. Ctr.

Sacramento, California, United States

Site Status

San Diego Cardiac Center

San Diego, California, United States

Site Status

Cardiovascular Consultants

Walnut Creek, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Delaware SPECT Imaging

Newark, Delaware, United States

Site Status

Florida Heart Associates

Fort Meyers, Florida, United States

Site Status

Diagnostic Cardiology, PA

Jacksonville, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Jacksonville Heart Center, PA

Jacksonville, Florida, United States

Site Status

Jacksonville Heart Center, PA

Jacksonville Beach, Florida, United States

Site Status

Heart and Vascular Institute of Florida

St. Petersburg, Florida, United States

Site Status

Cardiac Disease Specialists

Atlanta, Georgia, United States

Site Status

Idaho Cardiology Associates

Boise, Idaho, United States

Site Status

Idaho Cardiology Associates

Meridian, Idaho, United States

Site Status

Fox Valley Cardiovascular Consultants

Aurora, Illinois, United States

Site Status

Saint Francis Hospital of Evanston

Evanston, Illinois, United States

Site Status

Condell Medical Center

Libertyville, Illinois, United States

Site Status

Iowa Heart Center

Des Moines, Iowa, United States

Site Status

Cardiovascular Associates

Louisville, Kentucky, United States

Site Status

Clinical Trials Management, LLC

Metairie, Louisiana, United States

Site Status

Androscoggin Cardiology Associates

Auburn, Maine, United States

Site Status

Cardiovascular Consultants of Maine, PA

Scarborough, Maine, United States

Site Status

Pentucket Medical Associates

Haverhill, Massachusetts, United States

Site Status

Cardiology Associates of Northern Mississippi

Tupelo, Mississippi, United States

Site Status

Cardiovascular Consultants, PC

Kansas City, Missouri, United States

Site Status

Albany Associates in Cardiology

Albany, New York, United States

Site Status

Brooklyn Nuclear SPECT Imaging

Brooklyn, New York, United States

Site Status

Mid-Valley Cardiology

Kingston, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Blue Stem Cardiology

Bartlesville, Oklahoma, United States

Site Status

Cardiology Consultants of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Cardiology Consultants of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Medical University of SC (MUSC)

Charleston, South Carolina, United States

Site Status

Heart Place

Dallas, Texas, United States

Site Status

Deaconess Medical Center

Spokane, Washington, United States

Site Status

Sudbury Regional Hospital

Greater Sudbury, Ontario, Canada

Site Status

Univ. of Ottawa Heart Insitute

Ottawa, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Mieres JH, Shaw LJ, Hendel RC, Miller DD, Bonow RO, Berman DS, Heller GV, Mieres JH, Bairey-Merz CN, Berman DS, Bonow RO, Cacciabaudo JM, Heller GV, Hendel RC, Kiess MC, Miller DD, Polk DM, Shaw LJ, Smanio PE, Walsh MN; Writing Group on Perfusion Imaging in Women. American Society of Nuclear Cardiology consensus statement: Task Force on Women and Coronary Artery Disease--the role of myocardial perfusion imaging in the clinical evaluation of coronary artery disease in women [correction]. J Nucl Cardiol. 2003 Jan-Feb;10(1):95-101. doi: 10.1067/mnc.2003.130362. No abstract available.

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Iskandrian AE, Heo J, Nallamothu N. Detection of coronary artery disease in women with use of stress single-photon emission computed tomography myocardial perfusion imaging. J Nucl Cardiol. 1997 Jul-Aug;4(4):329-35. doi: 10.1016/s1071-3581(97)90111-2. No abstract available.

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Hachamovitch R, Berman DS, Kiat H, Bairey CN, Cohen I, Cabico A, Friedman J, Germano G, Van Train KF, Diamond GA. Effective risk stratification using exercise myocardial perfusion SPECT in women: gender-related differences in prognostic nuclear testing. J Am Coll Cardiol. 1996 Jul;28(1):34-44. doi: 10.1016/0735-1097(96)00095-2.

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Reference Type BACKGROUND
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Hachamovitch R, Berman DS, Kiat H, Cohen I, Friedman JD, Shaw LJ. Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms: an evaluation of incremental prognostic value and cost-effectiveness. Circulation. 2002 Feb 19;105(7):823-9. doi: 10.1161/hc0702.103973.

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Galassi AR, Azzarelli S, Tomaselli A, Giosofatto R, Ragusa A, Musumeci S, Tamburino C, Giuffrida G. Incremental prognostic value of technetium-99m-tetrofosmin exercise myocardial perfusion imaging for predicting outcomes in patients with suspected or known coronary artery disease. Am J Cardiol. 2001 Jul 15;88(2):101-6. doi: 10.1016/s0002-9149(01)01601-0.

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Marwick TH, Shaw LJ, Lauer MS, Kesler K, Hachamovitch R, Heller GV, Travin MI, Borges-Neto S, Berman DS, Miller DD. The noninvasive prediction of cardiac mortality in men and women with known or suspected coronary artery disease. Economics of Noninvasive Diagnosis (END) Study Group. Am J Med. 1999 Feb;106(2):172-8. doi: 10.1016/s0002-9343(98)00388-x.

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Shaw LJ, Heller GV, Travin MI, Lauer M, Marwick T, Hachamovitch R, Berman DS, Miller DD. Cost analysis of diagnostic testing for coronary artery disease in women with stable chest pain. Economics of Noninvasive Diagnosis (END) Study Group. J Nucl Cardiol. 1999 Nov-Dec;6(6):559-69. doi: 10.1016/s1071-3581(99)90091-0.

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Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM, Grunwald MA, Levy D, Lytle BW, O'Rourke RA, Schafer WP, Williams SV. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina). Circulation. 1999 Jun 1;99(21):2829-48. doi: 10.1161/01.cir.99.21.2829. No abstract available.

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Reference Type BACKGROUND

Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS; American Heart Association Writing Group on Myocardial Segmentation and Registration for Cardiac Imaging. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002 Jan 29;105(4):539-42. doi: 10.1161/hc0402.102975. No abstract available.

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Shaw LJ, Mieres JH, Hendel RH, Boden WE, Gulati M, Veledar E, Hachamovitch R, Arrighi JA, Merz CN, Gibbons RJ, Wenger NK, Heller GV; WOMEN Trial Investigators. Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial. Circulation. 2011 Sep 13;124(11):1239-49. doi: 10.1161/CIRCULATIONAHA.111.029660. Epub 2011 Aug 15.

Reference Type DERIVED
PMID: 21844080 (View on PubMed)

Related Links

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http://www.acc.org/clinical/guidelines/exercise/dirIndex.htm

ACC/AHA 2002 guideline update for exercise testing: a report of the American College of Cardiology/American Heart Association task Force on Practice Guidelines (Committee of Exercise Testing)

Other Identifiers

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The WOMEN study

Identifier Type: -

Identifier Source: secondary_id

HELL001524HE

Identifier Type: -

Identifier Source: org_study_id