The WOMEN Study: What is the Optimal Method for Ischemia Evaluation in WomeN?
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|ClinicalTrials.gov Identifier: NCT00282711|
Recruitment Status : Completed
First Posted : January 27, 2006
Last Update Posted : August 1, 2012
|Condition or disease|
|Coronary Artery Disease Heart Disease Coronary Arteriosclerosis Cardiovascular Disease Myocardial Ischemia|
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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.
|Study Type :||Observational|
|Actual Enrollment :||824 participants|
|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 Start Date :||June 2004|
|Actual Primary Completion Date :||December 2008|
|Actual Study Completion Date :||December 2010|
Standard Exercise treadmill test
Exercise treadmill testing with nuclear imaging
- 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. [ Time Frame: 2 years ]
- To evaluate the differential prognostic accuracy of normal exercise myocardial perfusion Tc-99m tetrofosmin SPECT against a normal exercise ECG. [ Time Frame: 2 years ]
- 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. [ Time Frame: 2 years ]
- Utility of the DASI questionnaire in determining which women are able to achieve predicted maximal heart rate response with treadmill testing [ Time Frame: 2 years ]
- Non-fatal myocardial infarction [ Time Frame: 2 years ]
- Unstable angina leading to revascularization [ Time Frame: 2 years ]
- Unstable angina with objective evidence of ischemia requiring hospitalization [ Time Frame: 2 years ]
- Cardiac death [ Time Frame: 2 years ]
- Hospitalization for heart failure [ Time Frame: 2 years ]
- Revascularization [ Time Frame: 2 years ]
- To provide objective information for developing guidelines for the evaluation of women at intermediate-high likelihood for CAD. [ Time Frame: 2 years ]
- A cost-effectiveness analysis will be performed comparing the various evaluation strategies. [ Time Frame: 2 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00282711
Show 43 Study Locations
|Principal Investigator:||Gary V. Heller, M.D., Ph.D.||Hartford Hospital, Hartford, CT|
|Principal Investigator:||Robert C. Hendel, M.D.||Rush University Medical Center, Chicago, IL|
|Principal Investigator:||Jennifer H. Mieres, M.D.||North SHore University Hospital, Long Island, NY|
|Principal Investigator:||Leslie J. Shaw, Ph.D.||Atlanta Cardiovascular Research Institute, Atlanta, GA|