Clinical trial NCT00282711: The WOMEN Study: What is the Optimal Method for Ischemia Evaluation in WomeN?
Official title: The WOMEN Study: What is the Optimal Method for Ischemia Evaluation in WomeN?"A Multi-Center, Prospective, Randomized Study to Establish the Optimal Method for Detection of CAD Risk in Women at an Intermediate-High Pre-Test Likelihood CAD"
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Heart Disease
Coronary Arteriosclerosis
Cardiovascular Disease
Myocardial Ischemia
Keywords: Diagnostic Techniques, Radioisotope
Radionuclide Imaging
Diagnostic Techniques, Cardiovascular
Heart Function tests
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: GE Healthcare
First posted: 2006-01-27
Enrollment: 824
Sex: FEMALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Females age 60 and above with suspected heart disease

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: To compare 2-year event rates for women capable of performing exercise treadmill testing with normal myocardial perfusion SPECT using Tc-99m tetrofosmin as compared with a negative stress ECG.
timeFrame: 2 years
Secondary outcomes:
measure: To evaluate the differential prognostic accuracy of normal exercise myocardial perfusion Tc-99m tetrofosmin SPECT against a normal exercise ECG.
timeFrame: 2 years
measure: To compare the diagnostic sensitivity and specificity of exercise ECG versus exercise ECG-gated Tc-99m tetrofosmin SPECT myocardial perfusion imaging in women who undergo an elective cardiac catheterization.
timeFrame: 2 years
measure: Utility of the DASI questionnaire in determining which women are able to achieve predicted maximal heart rate response with treadmill testing
timeFrame: 2 years
measure: Non-fatal myocardial infarction
timeFrame: 2 years
measure: Unstable angina leading to revascularization
timeFrame: 2 years
measure: Unstable angina with objective evidence of ischemia requiring hospitalization
timeFrame: 2 years
measure: Cardiac death
timeFrame: 2 years
measure: Hospitalization for heart failure
timeFrame: 2 years
measure: Revascularization
timeFrame: 2 years
measure: To provide objective information for developing guidelines for the evaluation of women at intermediate-high likelihood for CAD.
timeFrame: 2 years
measure: A cost-effectiveness analysis will be performed comparing the various evaluation strategies.
timeFrame: 2 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Southwest Heart
state: Arizona
city: Anaheim
country: United States
facility: Cardiology Consultants of Orange Country Medical Group, Inc
state: California
city: Escondido
country: United States
facility: Escondido Cardiology Associates
state: California
city: Mission Viejo
country: United States
facility: Mission Internal Medical Group
state: California
city: Orange
country: United States
facility: St. Joseph's Hospital Women's Hrt Cnt
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: Sacramento
country: United States
facility: Sacramento Heart & Vascular Res. Ctr.
state: California
city: San Diego
country: United States
facility: San Diego Cardiac Center
state: California
city: Walnut Creek
country: United States
facility: Cardiovascular Consultants
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Newark
country: United States
facility: Delaware SPECT Imaging
state: Delaware
city: Fort Meyers
country: United States
facility: Florida Heart Associates
state: Florida
city: Jacksonville Beach
country: United States
facility: Jacksonville Heart Center, PA
state: Florida
city: Jacksonville
country: United States
facility: Diagnostic Cardiology, PA
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Heart Center, PA
state: Florida
city: St Petersburg
country: United States
facility: Heart and Vascular Institute of Florida
state: Florida
city: Atlanta
country: United States
facility: Cardiac Disease Specialists
state: Georgia
city: Boise
country: United States
facility: Idaho Cardiology Associates
state: Idaho
city: Meridian
country: United States
facility: Idaho Cardiology Associates
state: Idaho
city: Aurora
country: United States
facility: Fox Valley Cardiovascular Consultants
state: Illinois
city: Evanston
country: United States
facility: Saint Francis Hospital of Evanston
state: Illinois
city: Libertyville
country: United States
facility: Condell Medical Center
state: Illinois
city: Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Louisville
country: United States
facility: Cardiovascular Associates
state: Kentucky
city: Metairie
country: United States
facility: Clinical Trials Management, LLC
state: Louisiana
city: Auburn
country: United States
facility: Androscoggin Cardiology Associates
state: Maine
city: Scarborough
country: United States
facility: Cardiovascular Consultants of Maine, PA
state: Maine
city: Haverhill
country: United States
facility: Pentucket Medical Associates
state: Massachusetts
city: Tupelo
country: United States
facility: Cardiology Associates of Northern Mississippi
state: Mississippi
city: Kansas City
country: United States
facility: Cardiovascular Consultants, PC
state: Missouri
city: Albany
country: United States
facility: Albany Associates in Cardiology
state: New York
city: Brooklyn
country: United States
facility: Brooklyn Nuclear SPECT Imaging
state: New York
city: Kingston
country: United States
facility: Mid-Valley Cardiology
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Bartlesville
country: United States
facility: Blue Stem Cardiology
state: Oklahoma
city: Philadelphia
country: United States
facility: Cardiology Consultants of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Cardiology Consultants of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of SC (MUSC)
state: South Carolina
city: Dallas
country: United States
facility: Heart Place
state: Texas
city: Spokane
country: United States
facility: Deaconess Medical Center
state: Washington
city: Ottawa
country: Canada
facility: Univ. of Ottawa Heart Insitute
state: Ontario
city: Sudbury
country: Canada
facility: Sudbury Regional Hospital
state: Ontario
Study officials:
affiliation: Hartford Hospital, Hartford, CT
name: Gary V. Heller, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center, Chicago, IL
name: Robert C. Hendel, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: North SHore University Hospital, Long Island, NY
name: Jennifer H. Mieres, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Atlanta Cardiovascular Research Institute, Atlanta, GA
name: Leslie J. Shaw, Ph.D.
role: PRINCIPAL_INVESTIGATOR
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citation: 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.