Representation of Women in Randomized Clinical Trials of Cardiovascular Disease Prevention
Abstract
Background— The 2007 American Heart Association guidelines for cardiovascular disease prevention in women drew heavily on results from randomized clinical trials; however, representation of women in trials of cardiovascular disease prevention has not been systematically assessed. Methods and Results— We abstracted 156 randomized clinical trials cited by the 2007 women’s prevention guidelines to determine female representation over time and by clinical indication, prevention type, location of trial conduct, and funding source. Both women and men were represented in 135 of 156 (86.5%) trials; 20 trials enrolled only men; 1 enrolled only women. Among all trials, the proportion of women increased significantly over time, from 9% in 1970 to 41% in 2006. Considering only trials that enrolled both women and men, female enrollment was 18% in 1970 and increased to 34% in 2006. Female representation was higher in international versus United States–only trials (32.7% versus 26.7%) and primary versus secondary prevention trials (42.6% versus 26.6%). Female enrollment was comparable in government/foundation-funded versus industry-funded trials (31.9% versus 31.5%). Representation of women was highest among trials in hypertension (44%), diabetes (40%), and stroke (38%) and lowest for heart failure (29%), coronary artery disease (25%), and hyperlipidemia (28%). By contrast, women accounted for 53% of all individuals with hypertension, 50% with diabetes, 51% with heart failure, 49% with hyperlipidemia, and 46% with coronary artery disease. Sex-specific results were discussed in only 31% of primary trial publications. Conclusions— Enrollment of women in randomized clinical trials has increased over time but remains low relative to their overall representation in disease populations. Efforts are needed to reach a level of representation that is adequate to ensure evidence-based sex-specific recommendations.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some treatments that currently exist for several diseases are not adequately evaluated in women, who are likely to be underrepresented in clinical trials, especially in Phases I and II.
“some of the treatments that currently exist for several diseases are not adequately evaluated in women27,28 who are likely to be underrepresented in clinical trials29,30, especially in Phases I and II31,32.”
From Sex and gender differences and biases in artificial intelligence for biomedicine and healthcare (2020) · cites this paper as [29]
Cites
Mosca, L., Benjamin, E. J., Berra, K., Bezanson, J. L., Dolor, R. J., Lloyd-Jones, D. M., Newby, L. K., Piña, I. L., Roger, V. L., Shaw, L. J., et al. (2011) · Circulation · doi:10.1161/cir.0b013e31820faaf8 · Cited by 2,143 · see citing works
Self-citationGender differences in the utilization of health care services.
Bertakis, K. D., Azari, R. S., Helms, L., Callahan, E. J., & Robbins, J. A. (2000) · PubMed · Cited by 1,469 · see citing works
Sex/Gender Differences in Cardiovascular Disease Prevention: What a Difference a Decade Makes
Mosca, L., Barrett-Connor, E., & Kass Wenger, N. (2011) · Circulation · doi:10.1161/circulationaha.110.968792 · Cited by 1,045 · see citing works
Boersma, E. H., Harrington, R. A., Moliterno, D. J., White, H. D., Théroux, P., de Werf, F. V., de Torbal, A., Armstrong, P. W., Wallentin, L. C., Wilcox, R. G., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07442-1 · Cited by 988 · see citing works
Insights From the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study
Merz, C. N. B., Shaw, L. J., Reís, S. E., Bittner, V., Kelsey, S. F., Olson, M. B., Johnson, B. D., Pepine, C. J., Mankad, S. V., Sharaf, B. L., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.12.084 · Cited by 849 · see citing works
Lee, P. Y. (2001) · JAMA · doi:10.1001/jama.286.6.708 · Cited by 848 · see citing works
Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men
Berger, J. S., Roncaglioni, M. C., Avanzini, F., Pangrazzi, I., Tognoni, G., & Brown, D. (2006) · JAMA · doi:10.1001/jama.295.3.306 · Cited by 781 · see citing works
Self-citationNational Study of Physician Awareness and Adherence to Cardiovascular Disease Prevention Guidelines
Mosca, L., Linfante, A. H., Benjamin, E. J., Berra, K., Hayes, S. N., Walsh, B. W., Fabunmi, R. P., Kwan, J., Mills, T., & Simpson, S. L. (2005) · Circulation · doi:10.1161/01.cir.0000154568.43333.82 · Cited by 757 · see citing works
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update
Mosca, L. J., Banka, C. L., Benjamin, E. J., Berra, K. A., Bushnell, C., Dolor, R. J., Ganiats, T. G., Gomes, A. S., Gornik, H. L., Gracia, C., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.02.020 · Cited by 749 · see citing works
Self-citationRepresentation of the Elderly, Women, and Minorities in Heart Failure Clinical Trials
Heiat, A., Gross, C. P., & Krumholz, H. M. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.15.1682 · Cited by 723 · see citing works
Insights From the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study
Shaw, L. J., Merz, C. N. B., Pepine, C. J., Reís, S. E., Bittner, V., Kelsey, S. F., Olson, M. B., Johnson, B. D., Mankad, S. V., Sharaf, B. L., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.01.072 · Cited by 719 · see citing works
Women and Ischemic Heart Disease
Shaw, L. J., Bugiardini, R., & Merz, C. N. B. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.098 · Cited by 662 · see citing works
Exploring the Biological Contributions to Human Health
Institute of Medicine (2001) · National Academies Press eBooks · doi:10.17226/10028 · Cited by 658 · see citing works
Blomkalns, A. L., Chen, A. Y., Hochman, J. S., Peterson, E. D., Trynosky, K. J., Diercks, D. B., Brogan, G. X., Boden, W. E., Roe, M. T., Ohman, E. M., et al. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.11.055 · Cited by 652 · see citing works
Self-citationEvidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update
Mosca, L. J., Banka, C. L., Benjamin, E. J., Berra, K. A., Bushnell, C., Dolor, R. J., Ganiats, T. G., Gomes, A. S., Gornik, H. L., Gracia, C., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.181546 · Cited by 579 · see citing works
Self-citationSex Differences in Medical Care and Early Death After Acute Myocardial Infarction
Jneid, H. M., Fonarow, G. C., Cannon, C. P., Hernandez, A. F., Palacios, I. F., Maree, A. O., Wells, Q. S., Bozkurt, B., LaBresh, K. A., Liang, L., et al. (2008) · Circulation · doi:10.1161/circulationaha.108.789800 · Cited by 575 · see citing works
Self-citationSex and Racial Differences in the Management of Acute Myocardial Infarction, 1994 through 2002
Vaccarino, V., Rathore, S. S., WENGER, N. K., Frederick, P. D., Abramson, J. L., Barron, H. V., Manhapra, A., Mallik, S., & Krumholz, H. M. (2005) · New England Journal of Medicine · doi:10.1056/nejmsa032214 · Cited by 543 · see citing works
The Exclusion of the Elderly and Women From Clinical Trials in Acute Myocardial Infarction
Gurwitz, J. H. (1992) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1992.03490110055029 · Cited by 532 · see citing works
Do Women Have More Adverse Drug Reactions?
Rademaker, M. (2001) · American Journal of Clinical Dermatology · doi:10.2165/00128071-200102060-00001 · Cited by 433 · see citing works
GELLER, S. E., Koch, A., Pellettieri, B. F., & Carnes, M. L. (2011) · Journal of Women s Health · doi:10.1089/jwh.2010.2469 · Cited by 373 · see citing works
Mosca, L. J., Greenberger, H. M., Dolor, R. J., Newby, L. K., & Robb, K. J. (2010) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.109.915538 · Cited by 360 · see citing works
Self-citationDrug Treatment of Hyperlipidemia in Women
Walsh, J. M. E. (2004) · JAMA · doi:10.1001/jama.291.18.2243 · Cited by 270 · see citing works
Harris, D. J., & Douglas, P. S. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008173430706 · Cited by 256 · see citing works
Self-citationHormones, genetic factors, and gender differences in cardiovascular disease
Rossouw, J. E. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00478-3 · Cited by 214 · see citing works
Sex Differences in Perceived Risks, Distrust, and Willingness to Participate in Clinical Trials
Ding, E. L. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.9.905 · Cited by 197 · see citing works
Mosca, L. J. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000121481.56512.c6 · Cited by 131 · see citing works
Dhruva, S. S. (2008) · Archives of Internal Medicine · doi:10.1001/archinternmed.2007.56 · Cited by 128 · see citing works
Ruhparwar, A. (2008) · Circulation · doi:10.1161/circulationaha.107.188511 · Cited by 108 · see citing works
Adherence to practice guidelines: The role of specialty society guidelines
Leape, L. L., Weissman, J. S., Schneider, E. C., Piana, R. N., Gatsonis, C. A., & Epstein, A. M. (2003) · American Heart Journal · doi:10.1067/mhj.2003.35 · Cited by 95 · see citing works
Gender Bias in Studies for Food and Drug Administration Premarket Approval of Cardiovascular Devices
Dhruva, S. S., Bero, L. A., & Redberg, R. F. (2011) · Circulation: Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.110.958215 · Cited by 87 · see citing works
LaPointe, N. M. A. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.14.1539 · Cited by 75 · see citing works
The Trials and Tribulations of Clinical Practice Guidelines
Cook, D. (1999) · JAMA · doi:10.1001/jama.281.20.1950 · Cited by 69 · see citing works
Willingness to Participate in Cardiac Trials
Peterson, E. D., Lytle, B. L., Biswas, M. S., & Coombs, L. P. (2004) · The American Journal of Geriatric Cardiology · doi:10.1111/j.1076-7460.2004.01709.x · Cited by 60 · see citing works
Long-term (5-Year) Changes in HDL Cholesterol in Cardiac Rehabilitation Patients
Warner, J. G., Brubaker, P. H., Zhu, Y. Y., Morgan, T. M., Ribisl, P. M., Miller, H. S., & Herrington, D. M. (1995) · Circulation · doi:10.1161/01.cir.92.4.773 · Cited by 58 · see citing works
Are women worrying about heart disease?
Biswas, M. S., Calhoun, P. S., Bosworth, H. B., & Bastian, L. A. (2002) · Women s Health Issues · doi:10.1016/s1049-3867(02)00136-6 · Cited by 52 · see citing works
Powell, J. H., Fleming, Y., Walker-McGill, C. L., & LeNoir, M. A. (2008) · Journal of the National Medical Association · doi:10.1016/s0027-9684(15)31206-2 · Cited by 49 · see citing works
Including Gender in Public Health Research
Phillips, S. P. (2011) · Public Health Reports · doi:10.1177/00333549111260s304 · Cited by 49 · see citing works
Falcon, R., Averitt, D., Currier, J. S., Squires, K., Hagins, D. P., Schaible, D. H., Ryan, R. J., & Mrus, O. B. O. T. G. S. J. (2011) · Journal of Women s Health · doi:10.1089/jwh.2010.2504 · Cited by 49 · see citing works
Who refuses enrollment in cardiac clinical trials?
Biswas, M. S., Newby, L. K., Bastian, L. A., Peterson, E. D., & Sugarman, J. (2007) · Clinical Trials · doi:10.1177/1740774507079434 · Cited by 35 · see citing works
Self-citationEuropean Medicines Agency policies for clinical trials leave women unprotected: Figure 1
Ruiz‐Cantero, M. T., & Pardo, M. A. (2006) · Journal of Epidemiology & Community Health · doi:10.1136/jech.2006.048769 · Cited by 28 · see citing works
Improving the quality of care for women with cardiovascular disease
Berger, J. S., Merz, C. N. B., Redberg, R. F., & Douglas, P. S. (2008) · American Heart Journal · doi:10.1016/j.ahj.2008.06.039 · Cited by 19 · see citing works
Self-citationPreventing recurrent coronary heart disease
van der Weijden, T., & Grol, R. (1998) · BMJ · doi:10.1136/bmj.316.7142.1400 · Cited by 17 · see citing works
Health-Related Quality of Life in the Gender, Race, And Clinical Experience Trial
Feinberg, J., Saag, M. S., Squires, K., Currier, J. S., Ryan, R. J., Coate, B., & Mrus, J. M. (2011) · AIDS Research and Treatment · doi:10.1155/2011/349165 · Cited by 12 · see citing works
Improving Women's Health Through Modernization of Our Bioinformatics Infrastructure
Oliva, A., Pinnow, E. E., Levin, R., et al. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100437 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sex and gender: modifiers of health, disease, and medicine
Mauvais-Jarvis, F., Bairey Merz, N., Barnes, P. J., Brinton, R. D., Carrero, J.-J., DeMeo, D. L., De Vries, G. J., Epperson, C. N., Govindan, R., Klein, S. L., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31561-0 · Cited by 2,001 · see citing works
Sex/Gender Differences in Cardiovascular Disease Prevention: What a Difference a Decade Makes
Mosca, L., Barrett-Connor, E., & Kass Wenger, N. (2011) · Circulation · doi:10.1161/circulationaha.110.968792 · Cited by 1,045 · see citing works
Kennedy-Martin, T., Curtis, S., Faries, D., Robinson, S., & Johnston, J. (2015) · Trials · doi:10.1186/s13063-015-1023-4 · Cited by 878 · see citing works
Hormone therapy for preventing cardiovascular disease in post-menopausal women
Boardman, H. M., Hartley, L., Eisinga, A., Main, C., Roqué i Figuls, M., Bonfill Cosp, X., Gabriel Sanchez, R., & Knight, B. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002229.pub4 · Cited by 612 · see citing works
Sex and gender differences in health: Science & Society Series on Sex and Science
Regitz‐Zagrosek, V. (2012) · The EMBO Reports · doi:10.1038/embor.2012.87 · Cited by 572 · see citing works
Sex and gender differences and biases in artificial intelligence for biomedicine and healthcare
Cirillo, D., Catuara-Solarz, S., Morey, C., Guney, E., Subirats, L., Mellino, S., Gigante, A., Valencia, A., Rementeria, M. J., Chadha, A. S., et al. (2020) · npj Digital Medicine · doi:10.1038/s41746-020-0288-5 · Cited by 553 · see citing works
Health equity among black women in the United States
Chinn, J. J., Martin, I. K., & Redmond, N. (2021) · Journal of Women's Health · doi:10.1089/jwh.2020.8868 · Cited by 320 · see citing works
Wenger, N. K. (2012) · Circulation · doi:10.1161/circulationaha.111.086892 · Cited by 176 · see citing works
Averitt, A. J., Weng, C., Ryan, P., & Perotte, A. (2020) · npj Digital Medicine · doi:10.1038/s41746-020-0277-8 · Cited by 137 · see citing works
Ball, J., Carrington, M. J., Wood, K. A., Stewart, S., & the SAFETY Investigators (2013) · PLoS ONE · doi:10.1371/journal.pone.0065795 · Cited by 98 · see citing works
Clemens, K. K., Woodward, M., Neal, B., & Zinman, B. (2020) · Diabetes Care · doi:10.2337/dc19-2257 · Cited by 70 · see citing works
Cardiovascular Disease in Women
Stock, E. O., & Redberg, R. (2012) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2012.07.001 · Cited by 65 · see citing works
Diagnosis and Treatment of Heart Disease: Are Women Different From Men?
Xhyheri, B., & Bugiardini, R. (2010) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2010.07.004 · Cited by 56 · see citing works
Ritzwoller, D. P., Sukhanova, A. S., Glasgow, R. E., Strycker, L. A., King, D. K., Gaglio, B., & Toobert, D. J. (2011) · Translational Behavioral Medicine · doi:10.1007/s13142-011-0037-z · Cited by 40 · see citing works
Gender, Cardiovascular Disease, and the Sexism of Obesity ∗
Bairey Merz, C. N., Andersen, H. S., & Shufelt, C. L. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.08.860 · Cited by 21 · see citing works
Batchelor, W. B., Damluji, A. A., Yong, C., Fiuzat, M., Barnett, S. D., Kandzari, D. E., Sherwood, M. W., Epps, K. C., Tehrani, B. N., Allocco, D. J., et al. (2021) · American Heart Journal · doi:10.1016/j.ahj.2021.02.003 · Cited by 7 · see citing works
- Authors
- Melloni, C., Berger, J. S., Wang, T. Y., Gunes, F., Stebbins, A., Pieper, K. S., Dolor, R. J., Douglas, P. S., Mark, D. B., & Newby, L. K.
- Affiliations
- Duke Medical Center (US)
- ORCID
- Venue
- Circulation: Cardiovascular Quality and Outcomes
- Published
- 2010-03
- Volume
- 3
- Issue
- 2
- Pages
- 135-142
- ISSN
- 1941-7705 (ISSN-L)
- 1941-7713
- OpenAlex
- W2139998668
- Cited by
- 455
- References
- 44
- Citations by year
- 2026: 11 · 2025: 26 · 2024: 28 · 2023: 23 · 2022: 33 · 2021: 42 · 2020: 34 · 2019: 21 · 2018: 42 · 2017: 21 · 2016: 23 · 2015: 27 · 2014: 27 · 2013: 34 · 2012: 31
- FWCI
- 30.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Cardiovascular Quality and Outcomes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Centre International de Recherche sur le Cancer
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Social Sciences › Gender Studies › Diversity and Career in Medicine
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Keywords
- women in clinical trials, cardiovascular disease prevention, gender representation, clinical trial recruitment, hypertension, diabetes mellitus, heart failure, coronary artery disease, hyperlipidemia, stroke, trial funding, American Heart Association guidelines
- MeSH terms
- Age Factors, American Heart Association, Cardiovascular Diseases, Drug Industry, Female, Financing, Government, Humans, Male, Primary Prevention, Research Support as Topic, Sex Factors, Time Factors, United States, Women's Health Services, Randomized Controlled Trials as Topic, Women's Health, Treatment Outcome, Practice Guidelines as Topic, Patient Selection, Evidence-Based Medicine, Research Subjects, Health Status Disparities, Secondary Prevention
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
