Sex-Specific Considerations in Guidelines Generation and Application

Abstract

New knowledge about maleefemale differences in pathophysiology, diagnosis, and treatment is shifting the practice of medicine from a one-size-fits all approach to a more individualized process that considers sex-specific interventions at the point of care. In this article, we review how clinical practice guideline committees can incorporate a structured framework to determine whether sex-specific assessments of the quality of the evidence or the particular recommendations should be made. The process can be operationalized by societies who author clinical practice guidelines by developing formal policies to approach biological sex in a systematic way, and by ensuring that writing committees include an individual who will champion the formal appraisal of the literature for associations between sex and the outcomes of interest. Ongoing challenges are discussed, and solutions are provided for how to disaggregate the evidence, how to assess bias, how to improve search strategies, and what to do when the data are Sex Matters in Cardiovascular DiseaseCardiovascular medicine is arguably most advanced in its understanding of clinically significant biologic differences between the sexes, from prevention to treatment. 3,4 Risk factors for heart disease and stroke are known to vary between men and women. 5,6 Clinical presentations of acute coronary syndrome differ, men experience earlier onset disease, and

Introducing the Canadian Women’s Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Diseases in Women

“…Gender refers to socially constructed roles, behaviors, expressions, and identities, and typically categorized as woman/girl or man/boy. Although Tannenbaum et al 5 report that CV medicine is arguably the most advanced specialty in its understanding of clinically significant biological differences between the sexes, from prevention to treatment, the lag time between discovery and implementation of sex-specific considerations accounts for disparities in CV morbidity and mortality.…”

“…6 The structural findings in the vasculopathy of women with ischemic heart disease demonstrate that both macro and micro vessels are smaller in size, have increased stiffness including fibrosis and remodeling, and have more diffuse disease whereby erosion is greater than plaque rupture. 5 Sex hormones are known to exert effects on the vascular reactivity via the endothelium and directly on smooth muscles. Very recently reported is the intriguing finding from longitudinal sex-specific analyses of blood pressure that women, compared with men, exhibit a steeper increase in blood pressure beginning as early as in the third decade and continuing through the life course, which suggests sex-unique biological characteristics of the vasculature, even independent of hormonal influence.…”

“…With the support of the American Heart Association, women-specific CV prevention guidelines were first published in 2004, 14 updated in 2007, 15 and subsequently updated as "effectiveness-based" guidelines in 2011. 16 Over the past decade, additional published guidelines, scientific statements, and advisories have increasingly addressed the following aspects of CVD in women: peripheral artery disease (2012), 5,17 trends in awareness of heart disease in women (2013), 18 stroke prevention in women (2014), 19 role of noninvasive testing in the clinical evaluation of women with suspected ischemic heart disease (2005) and updated in 2014, 20,21 acute myocardial infarction (2016), prevention and experience of ischemic heart disease (2016), 22 spontaneous coronary artery dissection (2018), 23 and promotion of risk identification and reduction of CVD in women through collaboration with obstetricians and gynecologists (2018). 24 All of these documents consistently report that the level of evidence is not available at this time to provide sex-based guidelines for treatment of heart events in women.…”

“…35,36 Tannenbaum et al offer a number of clinical examples in which the consequences of not including evidence separately in CPGs about women and men can range from missed opportunities to incorrect prescription of drugs. 5 If quality of care for both male and female patients is to be enhanced, sex and gender differences must be incorporated into CPG development. Our own research into the lack of sex-and gender-specific guidelines identified the following barriers to the addition of sex and gender considerations in the process of guideline development: (1) an inclination for working groups to develop recommendations for the "general" patient population; (2) a lack of cognizance that attention to sex-and gender-related factors may improve the quality of the guidelines; and (3) the absence of a organized process for identifying and systematically evaluating the evidence on sex and gender differences.…”

Sex as a Key Variable in Predicting Cardiovascular Outcomes: Rapidly Evolving Knowledge but Much More Needed

“…3 Although gender-vs sex-related determinants are often not well discriminated, both have major impacts that need to be considered in clinical decision making; however, there is a dearth of data to allow the effective generation of sex-related clinical management guidelines. 4 Low participation of women in trials, an unfortunate tendency to assume superficially that drug and device safety and efficacy are the same in both sexes, lack of focus on sex-specific risk factors, and psychosocial determinants of health are among the many factors responsible for the insufficiency of data.…”