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

Coronary Artery Disease Clinical Trial

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"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282711
• Other study ID #: HELL001524HE
• Secondary ID: The WOMEN study
• Status: Completed
• Phase: N/A
• First received: January 25, 2006
• Last updated: July 31, 2012
• Start date: June 2004
• Est. completion date: December 2010

Study information

• Verified date: July 2012
• Source: Hartford Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 824
• Est. completion date: December 2010
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Arteriosclerosis
• Cardiovascular Disease
• Cardiovascular Diseases
• Coronary Arteriosclerosis
• Coronary Artery Disease
• Coronary Disease
• Heart Disease
• Ischemia
• Myocardial Ischemia

Locations

Country	Name	City	State
Canada	Univ. of Ottawa Heart Insitute	Ottawa	Ontario
Canada	Sudbury Regional Hospital	Sudbury	Ontario
United States	Albany Associates in Cardiology	Albany	New York
United States	Cardiology Consultants of Orange Country Medical Group, Inc	Anaheim	California
United States	Cardiac Disease Specialists	Atlanta	Georgia
United States	Androscoggin Cardiology Associates	Auburn	Maine
United States	Fox Valley Cardiovascular Consultants	Aurora	Illinois
United States	Blue Stem Cardiology	Bartlesville	Oklahoma
United States	Idaho Cardiology Associates	Boise	Idaho
United States	Brooklyn Nuclear SPECT Imaging	Brooklyn	New York
United States	Medical University of SC (MUSC)	Charleston	South Carolina
United States	Heart Place	Dallas	Texas
United States	Iowa Heart Center	Des Moines	Iowa
United States	Escondido Cardiology Associates	Escondido	California
United States	Saint Francis Hospital of Evanston	Evanston	Illinois
United States	Florida Heart Associates	Fort Meyers	Florida
United States	Hartford Hospital	Hartford	Connecticut
United States	Pentucket Medical Associates	Haverhill	Massachusetts
United States	Diagnostic Cardiology, PA	Jacksonville	Florida
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Jacksonville Heart Center, PA	Jacksonville	Florida
United States	Jacksonville Heart Center, PA	Jacksonville Beach	Florida
United States	Cardiovascular Consultants, PC	Kansas City	Missouri
United States	Mid-Valley Cardiology	Kingston	New York
United States	Condell Medical Center	Libertyville	Illinois
United States	Cardiovascular Associates	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	Idaho Cardiology Associates	Meridian	Idaho
United States	Clinical Trials Management, LLC	Metairie	Louisiana
United States	Mission Internal Medical Group	Mission Viejo	California
United States	Delaware SPECT Imaging	Newark	Delaware
United States	St. Joseph's Hospital Women's Hrt Cnt	Orange	California
United States	Cardiology Consultants of Philadelphia	Philadelphia	Pennsylvania
United States	Cardiology Consultants of Philadelphia	Philadelphia	Pennsylvania
United States	Sutter Roseville Medical Center	Roseville	California
United States	Sacramento Heart & Vascular Res. Ctr.	Sacramento	California
United States	San Diego Cardiac Center	San Diego	California
United States	Cardiovascular Consultants of Maine, PA	Scarborough	Maine
United States	Deaconess Medical Center	Spokane	Washington
United States	Heart and Vascular Institute of Florida	St Petersburg	Florida
United States	Southwest Heart	Tucson	Arizona
United States	Cardiology Associates of Northern Mississippi	Tupelo	Mississippi
United States	Cardiovascular Consultants	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Hartford Hospital	GE Healthcare

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (21)

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. Review. — View Citation

Chaitman BR, Bourassa MG, Davis K, Rogers WJ, Tyras DH, Berger R, Kennedy JW, Fisher L, Judkins MP, Mock MB, Killip T. Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circulation. 1981 Aug;64(2):360-7. — View Citation

Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979 Jun 14;300(24):1350-8. — View Citation

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. — View Citation

Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD, Winters WL Jr, Yanowitz FG, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Lewis RP, O'Rourke RA, Ryan TJ. ACC/AHA guidelines for exercise testing: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). Circulation. 1997 Jul 1;96(1):345-54. — View Citation

Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters WL Jr, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC Jr; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation. 2002 Oct 1;106(14):1883-92. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Hlatky MA, Pryor DB, Harrell FE Jr, Califf RM, Mark DB, Rosati RA. Factors affecting sensitivity and specificity of exercise electrocardiography. Multivariable analysis. Am J Med. 1984 Jul;77(1):64-71. — View Citation

Holdright DR, Fox KM. Characterization and identification of women with angina pectoris. Eur Heart J. 1996 Apr;17(4):510-7. Review. Erratum in: Eur Heart J 1996 Sep;17(9):1452. — View Citation

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. Review. — View Citation

Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol. 1999 Mar 1;83(5):660-6. — View Citation

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. — View Citation

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. Review. Erratum in: J Nucl Cardiol. 2003 Mar-Apr;10(2):218. — View Citation

Mosca L, Grundy SM, Judelson D, King K, Limacher M, Oparil S, Pasternak R, Pearson TA, Redberg RF, Smith SC Jr, Winston M, Zinberg S. Guide to Preventive Cardiology for Women.AHA/ACC Scientific Statement Consensus panel statement. Circulation. 1999 May 11;99(18):2480-4. Review. — View Citation

Pancholy SB, Fattah AA, Kamal AM, Ghods M, Heo J, Iskandrian AS. Independent and incremental prognostic value of exercise thallium single-photon emission computed tomographic imaging in women. J Nucl Cardiol. 1995 Mar-Apr;2(2 Pt 1):110-6. — View Citation

Santana-Boado C, Candell-Riera J, Castell-Conesa J, Aguadé-Bruix S, García-Burillo A, Canela T, González JM, Cortadellas J, Ortega D, Soler-Soler J. Diagnostic accuracy of technetium-99m-MIBI myocardial SPECT in women and men. J Nucl Med. 1998 May;39(5):751-5. — View Citation

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. — View Citation

Shaw LJ, Hendel R, Borges-Neto S, Lauer MS, Alazraki N, Burnette J, Krawczynska E, Cerqueira M, Maddahi J; Myoview Multicenter Registry. Prognostic value of normal exercise and adenosine (99m)Tc-tetrofosmin SPECT imaging: results from the multicenter registry of 4,728 patients. J Nucl Med. 2003 Feb;44(2):134-9. Erratum in: J Nucl Med. 2003 Apr;44(4):648. — View Citation

Shaw LJ, Miller DD, Romeis JC, Kargl D, Younis LT, Chaitman BR. Gender differences in the noninvasive evaluation and management of patients with suspected coronary artery disease. Ann Intern Med. 1994 Apr 1;120(7):559-66. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		2 years	No
Secondary	To evaluate the differential prognostic accuracy of normal exercise myocardial perfusion Tc-99m tetrofosmin SPECT against a normal exercise ECG.		2 years	No
Secondary	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.		2 years	No
Secondary	Utility of the DASI questionnaire in determining which women are able to achieve predicted maximal heart rate response with treadmill testing		2 years	No
Secondary	Non-fatal myocardial infarction		2 years	No
Secondary	Unstable angina leading to revascularization		2 years	No
Secondary	Unstable angina with objective evidence of ischemia requiring hospitalization		2 years	No
Secondary	Cardiac death		2 years	No
Secondary	Hospitalization for heart failure		2 years	No
Secondary	Revascularization		2 years	No
Secondary	To provide objective information for developing guidelines for the evaluation of women at intermediate-high likelihood for CAD.		2 years	No
Secondary	A cost-effectiveness analysis will be performed comparing the various evaluation strategies.		2 years	No