Despite differences in biology that influence disease incidence, drug metabolism, and response to therapies, women remain under-enrolled in cardiovascular clinical trials. Estimates regarding ...treatment efficacy and safety are derived from male-predominant trial populations, with inadequate balance between sex subgroups for meaningful analysis on sex-specific treatment effects. Treatment strategies for women, particularly women of childbearing years, are derived from trials with predominantly men participants, from lower quality, observational studies, or anecdotal evidence. Guideline recommendations for women who are pregnant or lactating are typically based on opinion as there is little evidence to guide them. In this review, we discuss trial design factors independently associated with the under-enrollment of women, identify possible strategies to increase the enrollment of women in trials, and suggest multi-level actions that could close sex-based research disparities. Recruiting and retaining women trialists, independently associated with increased enrollment of women and Black, Indigenous, and Persons of Color (BIPOC) participants, and diversifying research teams may be effective approaches. Modifying trial design by eliminating default sex-specific exclusion criteria, developing patient-centered consent and participation processes, incorporating pragmatic follow-up schemes, and incorporating sex/gender analysis into trial planning may also increase the enrollment of women participants. Journals and funding bodies should require trials to report participant to prevalence ratios, sex-disaggregated trial flow, and sex-treatment interactions. Healthcare systems can help create research-ready cultures that both enhance patient engagement in trials and expedite end-of-trial knowledge translation.
•Women are under-enrolled in cardiovascular trials, limiting trial generalizability.•Trials should address design factors associated with under-enrollment of women.•Journals and funding bodies should require sex representation and analysis.
Cardiovascular diseases (CVDs) are responsible for approximately 35% of all deaths in women. In 2019, the global age-standardized CVD prevalence and mortality of women were 6,403 per 100,000 and 204 ...per 100,000, respectively. Although the age- and population-adjusted prevalence has decreased globally, opposite trends are evident in regions of socioeconomic deprivation. Cardiovascular health and outcomes are influenced by regional socioeconomic, environmental, and community factors, in addition to health care system and individual factors. Cardiovascular care in women is commonly plagued by delayed diagnoses, undertreatment, and knowledge gaps, particularly in women-specific or women-predominant conditions. In this paper, we describe the global epidemiology of CVD and highlight multilevel determinants of cardiometabolic health. We review knowledge and health care gaps that serve as barriers to improving CVD outcomes in women. Finally, we present national, community, health care system, and research strategies to comprehensively address cardiometabolic risk and improve outcomes in women.
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•CVD is the leading cause of death in women worldwide.•Regional variation in CVD burden reflects socioeconomic determinants.•A multilevel approach is required to improve cardiometabolic health and CVD outcomes in women on a global scale.
Cardiovascular diseases (CVDs) are responsible for approximately 35% of all deaths in women. In 2019, the global age-standardized CVD prevalence and mortality of women were 6,403 per 100,000 and 204 ...per 100,000, respectively. Although the age- and population-adjusted prevalence has decreased globally, opposite trends are evident in regions of socioeconomic deprivation. Cardiovascular health and outcomes are influenced by regional socioeconomic, environmental, and community factors, in addition to health care system and individual factors. Cardiovascular care in women is commonly plagued by delayed diagnoses, undertreatment, and knowledge gaps, particularly in women-specific or women-predominant conditions. In this paper, we describe the global epidemiology of CVD and highlight multilevel determinants of cardiometabolic health. We review knowledge and health care gaps that serve as barriers to improving CVD outcomes in women. Finally, we present national, community, health care system, and research strategies to comprehensively address cardiometabolic risk and improve outcomes in women.Cardiovascular diseases (CVDs) are responsible for approximately 35% of all deaths in women. In 2019, the global age-standardized CVD prevalence and mortality of women were 6,403 per 100,000 and 204 per 100,000, respectively. Although the age- and population-adjusted prevalence has decreased globally, opposite trends are evident in regions of socioeconomic deprivation. Cardiovascular health and outcomes are influenced by regional socioeconomic, environmental, and community factors, in addition to health care system and individual factors. Cardiovascular care in women is commonly plagued by delayed diagnoses, undertreatment, and knowledge gaps, particularly in women-specific or women-predominant conditions. In this paper, we describe the global epidemiology of CVD and highlight multilevel determinants of cardiometabolic health. We review knowledge and health care gaps that serve as barriers to improving CVD outcomes in women. Finally, we present national, community, health care system, and research strategies to comprehensively address cardiometabolic risk and improve outcomes in women.
Abstract
Participants enrolled in cardiovascular disease (CVD) randomized controlled trials are not often representative of the population living with the disease. Older adults, children, women, ...Black, Indigenous and People of Color, and people living in low- and middle-income countries are typically under-enrolled in trials relative to disease distribution. Treatment effect estimates of CVD therapies have been largely derived from trial evidence generated in White men without complex comorbidities, limiting the generalizability of evidence. This review highlights barriers and facilitators of trial enrollment, temporal trends, and the rationale for representativeness. It proposes strategies to increase representativeness in CVD trials, including trial designs that minimize the research burden on participants, inclusive recruitment practices and eligibility criteria, diversification of clinical trial leadership, and research capacity-building in under-represented regions. Implementation of such strategies could generate better and more generalizable evidence to reduce knowledge gaps and position the cardiovascular trial enterprise as a vehicle to counter existing healthcare inequalities.
Graphical Abstract
Graphical Abstract
Barriers to enrollment of diverse populations and strategies to achieve representative enrollment in cardiovascular clinical trials.
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