EACTS 2021: Panel urges action over lack of representation of women in coronary revascularisation trials

Roxana Mehran (right) presents virtually at EACTS 2021

The underrepresentation of women in clinical coronary revascularisation trials may encourage treatment that favours outcomes in men, despite the presence of significant differences in the clinical characteristics between women and men. This is according to speakers at the European Society of Cardio-Thoracic Surgery annual meeting (EACTS 2021; 13–16 October; Barcelona, Spain and virtual) in a panel session which considered current data concerning women undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

“We as women are not small men, and there are a lot of pathobiological differences in how we present, what the anatomy looks like and how we respond to different therapeutic regimens or revacsularisation strategies,” said interventional cardiologist Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA) who opened the session with a presentation detailing the differences between women and men undergoing PCI.

“I think it is really important to think about how myocardial ischaemia could be very different in its presentation, in its lesion and vessel characteristics, between men and women,” Mehran added. Detailing some potential differences that may be present between women and men, she listed smaller vessel size, higher risk of restenosis, lower plaque burden, diffuse disease, more slow flow mediated dilation,  and higher fractional flow reserve (FFR).

Mehran told EACTS attendees that women presenting to the cath lab are often a lot older than men, and are more likely to have more comorbidities such as diabetes, hypertension and hypolipidemia. Furthermore, Mehran said that women may be at a higher risk for bleeding complications than men, sharing data from her centre suggesting that high bleeding risk criteria are seen in around 56% of women, compared to 40% of men coming to the cath lab.

But, despite these characteristic differences, treatment guidelines do not reflect any difference in terms of recommendations for treatment between men and women, she added. “The strategies are not tailored according to sex, and I wonder if we should be having an entire section in our guidelines that relates to the sex differences. I think the time has come for us to think about that,” Mehran commented.

Women have made up around 20–25% of the patient population in major drug-eluting stent studies, Mehran said, later commenting that “there is no question we have to be better represented”.

Mehran’s comments regarding differences in outcomes for women undergoing PCI painted a similar picture to those of the following speaker, cardiac surgeon Sigrid Sandner (Medical University of Vienna, Vienna, Austria), who discussed the differences in CABG outcomes between women and men. The proportion of women in the CABG population is between 20–30% , Sandner said, and she noted that there are significant differences in the clinical characteristics seen in women and men undergoing CABG.

Women tend to present at a more advanced age than men, and they present more frequently in urgent or emergency status, Sandner explained, adding that they tend to come with a higher burden of comorbidities such as hypertension, diabetes, peripheral vascular disease and renal dysfunction, and are more likely to present with heart failure symptoms, despite actually having better left ventricular systolic function than men. “We know that women tend to have smaller calibre coronary artery targets and also smaller arterial grafts,” she added, as well as noting that women frequently face delayed diagnosis and delayed referral for surgery.

Sigrid Sandner

She continued: “Women are, as Dr Mehran said, underrepresented in clinical trials of cardiovascular care, and particularly in clinical trials of cardiovascular surgery. The participation prevalence ratio also for women in CABG trials has consistently been between 0.5–0.6 and this reflects a very poor representation of women in CABG trials. It raises the question of the applicability of the trial results to both sexes, and it also raises the question of whether there are potentially differential sex-based treatment effects.”

She then turned to differences in outcomes between men and women undergoing CABG, commenting that there are likely to be a multitude of factors influencing these disparities.

“We know that women have a higher burden of comorbidities, but even after we adjust for this and for presentation these differences in outcome remain, so there may be an underlying biological mechanism,” Sandner said. “What we also see is that there are disparities in operative technique, particularly as they relate to the use of arterial grafts, the use of cardiopulmonary bypass and the completeness of revascularisation.”

Sandner cited the findings of a study, first presented at the 57th Annual Meeting of The Society of Thoracic Surgeons (STS 2021, 29–31 January, virtual) which analysed detailed demographic, clinical, and procedural data from more than 1.2 million patients, using data from the STS Adult Cardiac Surgery Database.

The study closely examined the correlation between female sex and the likelihood of receiving one of the three different CABG surgical techniques that are recommended in official US and European guidelines—grafting of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery, complete revascularisation, and multiarterial grafting. Results showed that women were 14‒22% less likely than men to undergo CABG procedures with these revascularisation strategies.

“What they showed was that women less frequently received LAD revascularisation with LIMA, and they had lower odds of receiving complete revascularisation or multiple arterial grafting. Although the evidence is conflicting on the effect on outcomes there is observational evidence that has shown that women do derive the same survival benefit from multiple arterial grafting as men,” Sandner commented.

Echoing Mehran’s call for a greater capture of female-specific data and clinical trials, in her concluding remarks Sandner commented: “We definitely need strategies to improve the outcomes after CABG in women, [and] we need better evidence of the surgical use of techniques and this includes multiple arterial grafting and off-pump CABG, and we may need sex-specific risk assessment scores. We definitely need a greater involvement of women in clinical trials, or clinical trials that are specifically designed to study outcomes in an exclusively female CABG population.”

ROMA Women

Though speakers had criticised the lack of clinical trials focused specifically on treatment and outcomes specifically in women, later in the session Mario Gaudino (New York-Presbyterian and Weill Cornell Medicine, New York, USA) offered attendees a glimpse of what he described as the first cardiac surgery trial dedicated to women.

Mario Gaudino at EACTS 2021

ROMA Women—a spin-off of the ROMA (Randomization of Single vs Multiple Arterial Grafts) study—is a global trial that will seek to randomise over 2,100 female patients undergoing primary isolated non-emergent CABG to either single or multiple arterial grafts. Enrolment is expected to be completed after 2022.

Building upon comments made earlier in the session, Gaudino’s presentation noted that most of the data on CABG are based upon studies taken from an overwhelmingly male population, with women representing around 20% of the patients enrolled in cardiac surgery trials published between 2000 and 2019, and pointing out that this number is “too small to derive estimates of treatment effects”. His presentation also noted that the proportion of women studied had dropped significantly during this period.

Study taking place exclusively among women is justified as there are surgical and biologic reasons to believe that the treatment effect may be different by sex and current recommendations may not be applicable to women, he said.

“The reality is that we have no solid information to inform our clinical decision-making for women undergoing coronary artery bypass surgery,” Gaudino commented.

He later added: “Everything is telling us that there are important differences between sexes and you as a community should better try to investigate those differences, rather than to rely on studies that have been performed in an overwhelmingly male population.”


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