Abstract
“Why are women undertreated relative to men? What characteristics make them so different from men when the physician is at the hospital bedside considering treatment?”
Despite advances in medical care that have resulted in a reduction in cardiovascular mortality, coronary heart disease remains the leading cause of death among women in the USA [1]. In the last two decades, several reports have highlighted significant gender disparities in diagnosis, management and outcomes across a spectrum of acute coronary syndromes (ACS) [2–8].
“Female representation is also lower in trials of coronary artery disease compared with other disease areas.”
An analysis from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the of the American College of Cardiology [ACC]/American Heart Association [AHA] Guidelines (CRUSADE) Quality Improvement Initiative demonstrated that although women with non-ST-segment elevation (NSTE) ACS presented with baseline characteristics associated with a greater risk of adverse clinical outcomes, they were treated less aggressively than men, received acute and discharge guideline-recommended treatments less often and underwent cardiac catheterization and subsequent revascularization less frequently [4]. Recent analyses have also demonstrated that the lower use of proven, early medical treatments and delayed reperfusion therapy can, in part, explain the higher rate of early death among women presenting with ST-segment elevation myocardial infarction (STEMI) [3,7]. However, more concerning is the evidence that treatment disparities have been present for decades and have not narrowed in recent years despite awareness of the presence of care disparities and opportunities to improve healthcare among women [5].
The following questions need addressing: why are women undertreated relative to men? What characteristics make them so different from men when the physician is at the hospital bedside considering treatment?
Multiple factors are likely to contribute to the lower use of evidence-based medicine and higher rates of cardiovascular complications among women with ACS. First, women suffering an ACS event tend to present more often with atypical symptoms, such as nausea, vomiting, fatigue, dyspnea and atypical pain locations, compared with men [9]. Second, cardiovascular disease affects women later in their lives. Among patients presenting with a NSTE ACS, the mean age is 62 years for men versus 68 years for women, and for those presenting with a STEMI, the mean age is 57 years for men versus 66 years for women. In addition to older age, women are also more likely to present with more comorbidities than men [4,5,8]. Third, delays in hospital presentation or in symptom recognition ultimately result in delays in diagnosis and effective treatment [4,8]. It has also been hypothesized that a patient's sex may influence a physician's recommendation with respect to cardiac catheterization regardless of the patient's clinical characteristics [2]. Finally, lack of solid data on cardiovascular disease management in women owing to their under-representation in randomized clinical trials (RCT) leaves uncertainty among clinicians regarding the risk–benefit balance of many treatments [10–12].
“Women do not recognize cardiovascular disease as a major concern, perhaps because they consider it a ‘man's disease’…”
Recent studies exploring female enrollment noted that women and the elderly still remain largely under-represented in cardiovascular clinical trials relative to their representation in the disease population worldwide, and that despite the release of specific legislation detailing the policy on women's representation, enrollment of female patients in RCTs has not significantly increased in the last decade; women still account for only 20–25% of the trial populations [10,11]. Female representation is also lower in trials of coronary artery disease compared with other disease areas [12]. Therefore, evidence of treatment effect among women presenting with ACS remains weak.
What can be done to address the problem?
Education is needed on multiple fronts. Women do not recognize cardiovascular disease as a major concern, perhaps because they consider it a ‘man's disease’ and are not aware that heart disease is the leading cause of death among their peers. An important downside of this lack of knowledge is that women who are not aware of cardiovascular risk factors do not take a critical look at their lifestyle, do not respond to symptoms of ischemia in a timely manner, or even worse, do not recognize the symptoms of heart attack at all. This lack of knowledge may also contribute to less interest in, or less willingness to participate in, clinical trials, from which evidence to support treatment of women originates. The AHA's ‘Go red for women’ campaign is a program targeted at educating women regarding their risk for heart disease, and will hopefully help to motivate them to change their lifestyle as well as their evaluation- and treatment-seeking behaviors. Better education provided to women by physicians concerning cardiovascular risk factors and symptoms that should alert women is also warranted.
“…the NIH Revitalization Act legally required inclusion of women and men in clinical trials to be consistent with the known sex-related prevalence of the disease under investigation…”
It is important to acknowledge what has been done so far. After the recognition of the presence of this wide gap between the quality of care delivered to men and women, several efforts that could address the potential reasons for disparity in the management of women with myocardial infarction have been developed. First, federal mandates have required increased enrollment of women, the elderly and other minorities in clinical trials in an attempt to guarantee adequate representation within these trials that will form the base of the evidence for new treatments and that will ultimately help to eliminate uncertainty with regard to the risks versus benefits of treatment in these populations. In 1993, the NIH Revitalization Act legally required inclusion of women and men in clinical trials to be consistent with the known sex-related prevalence of the disease under investigation in order to provide appropriate data on the efficacy of treatments for both sexes. In 2001, a further step toward understanding the differences between sexes was promoted by the report ‘Exploring the Biological Contribution to Human Health: Does Sex Matter’ launched by the Institute of Medicine (Washington, DC, USA), with the goal of translating these differences into practice [13]. At the same time, the NIH has reinforced the existing Federal legal requirements for inclusion of women in all NIH-sponsored research, as well as the requirements for analyses of outcomes by sex [14]. Moreover, a national research institute has been created by the Canadian Institutes of Health Research with the commitment of studying biological factors (sex) and sociocultural experiences (gender) that influence health [15].
In March 2007, Duke Clinical Research Institute convened a ‘Think Tank’ meeting of experts on heart disease in women with the goal of finding possible solutions to improve the quality of care for women with heart disease. Among the proposed strategies were [16]:
Implementation of prespecified analytical plans in trial design for dealing with sex-specific data;
Increased female enrollment in randomized clinical trials using recruitment strategies that were successful in prior studies;
Mandatory reporting of primary and secondary results by sex.
Finally, in the last decade, the AHA and the ACC have instituted quality improvement programs and developed performance measures in order to document clinically relevant quality indicators in the treatment of patients with STEMI and NSTEMI, as well as to promote quality improvement nationally [3,8]. These programs use standardized data collection forms to collect use of class I guideline-recommended therapies at hospital admission and discharge and secondary prevention plans, and provide feedback on performance to each site participating in the quality improvement initiative to be used as educational tools. Recent analyses have demonstrated that through these programs substantial improvements in the quality of care delivered have been achieved [3,17,18].
Therefore, both women's education and broadening the evidence on cardiovascular treatments in women are needed to close the gap impairing optimal care of cardiovascular disease in women.
Footnotes
Details regarding the disclosure can be found at www.dcri.duke.edu/research/documents/Newby-COI.pdf.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.