Clinical trials in cardiothoracic surgery must ensure that sufficient numbers of women are enrolled to adequately reflect differences between the sexes, attendees of the 2022 European Association of Cardio-Thoracic Surgery (EACTS) annual meeting (5–8 October, Milan Italy) have heard.
This was the message of Jolanda Kluin (University of Amsterdam, Amsterdam, The Netherlands) during a plenary session entitled ‘Clinical trials in coronary surgery–a look into the future’ in which she made the case for a revascularisation trial focused on women.
“Historically, most medical research has been conducted in predominantly male populations and the results from those studies were assumed to be equal between men and women, but there is increasing evidence that this is not the case,” Kluin said in her presentation.
Making her case in favour of a coronary revascularisation trial for women, Kluin detailed that there are numerous differences between men and women relating to cardiovascular disease, including in symptoms, risk factors, and treatment. Regarding the latter she offered diabetes as an example of an important difference between men and women. “In a non-diabetic population, women have a third of the risk of developing myocardial infarction compared to men. But, if they both have diabetes, we see that women have half the risk. Currently, diabetes is a more important risk factor in the female population as the male population.”
Further to these points, Kluin also noted that there is growing evidence of differences in outcomes of coronary artery bypass graft (CABG) surgery between the sexes, pointing to a pooled analysis of individual patient data, compiled by Mario Gaudino (Weill Cornell Medicine, New York) et al and published in the European Heart Journal which reached the conclusion that women have worse outcomes than men in the first five years after the procedure.
Speculating on the factors behind this difference, Kluin reflected that there are “multifactorial” underlying causes, suggesting that female patients are more likely to be diagnosed later and therefore face more severe disease, she pointed to anatomical differences—such as smaller coronary arteries—that may make surgery more complicated, and noted differences in hormones, renal function, and coagulation that may also have a bearing. It is interesting to see that female sex is a risk factor in the Euroscore and nobody has really questioned this, Kluin commented. “What if a bald man or a male patient with blue eyes would have a higher risk of mortality after cardiac surgery. Would we just accept that?” she questioned.
“There are important differences between men and women in the presentation, symptoms, risk factors, anatomy and the outcome of cardiovascular disease,” Kluin said in the concluding remarks of her presentation. “Large databases should be exploited to address sex differences and to improve women’s health. If you perform a clinical study, ensure that sufficient numbers of women and men are included and take a sex disaggregated approach to collect, analyse and report your data.”
Among the action that is being taken to address this disparity, Kluin highlighted ROMA Women—a spin-off of the ROMA (Randomization of Single vs Multiple Arterial Grafts) study—a global trial that randomising female patients undergoing primary isolated non-emergent CABG to either single or multiple arterial grafts, which is being led by Gaudino.
Responding to Kluin’s presentation, EACTS secretary general J Rafael Sádaba (Hospital Universitario de Navarra, Pamplona, Spain), who was moderating the session, said: “It is a wake-up call to take this in mind for future trials.”
