A historic underrepresentation of women in clinical trials for coronary artery bypass graft (CABG) surgery has contributed to a disparity in outcomes between men and women, delegates at the 2023 European Association of Cardio-Thoracic Surgery (EACTS) annual meeting (4–7 October, Vienna, Austria) heard.
This was among the messages from a session titled ‘Improving CABG outcomes in women: A call to action’, during which speakers tackled the imbalance of available data concerning CABG outcomes in women, the need for dedicated coronary surgery trials for women, and future strategies to improve outcomes
“When we talk about disparities in outcomes of CABG between women and men, what we need to recognise is that in the treatment of coronary disease in women there is a disparity along every step of the way—from preoperative to postoperative—that contributes to these differences in outcomes that we are seeing,” Sigrid Sandner (Medical University of Vienna, Vienna, Austria) said in her opening presentation.
Sandner’s presentation set the tone for the session and highlighted some of the existing data to detail disparities in care among patients receiving coronary bypass surgery. She pointed to analysis from the Society of Thoracic Surgeons (STS) database, showing that women less frequently receive a left internal mammary artery (LIMA) graft to the left anterior descending artery, less frequently receive multiple arterial grafting, and were also less likely to undergo complete anatomic revascularisation than men.
Sandner also drew on the findings of a retrospective cohort study of over one million US patients, published earlier this year in JAMA Surgery, in which women were found to have a significantly higher risk of operative mortality and postoperative complications after isolated CABG when compared with men.
Importantly, said Sandner, who was a co-author on the paper alongside another of the session’s speakers, Mario Gaudino (Weill Medical College, New York, USA), the research also showed that there had been no change in excess operative risk for women between 2011 and 2020, the entire period of the study.
“Women had increased operative mortality and morbidity compared with men in every single year across the entire study period,” she said. “There was also an attributable risk for female sex. It is a very elaborate statistical analysis, but what it basically gives you is the added risk of female sex on top of baseline risk. This was present for mortality and morbidity, across the study period, and it has remained largely unchanged over the past decade.”
Multiple arterial challenges
Following Sandner, Jennifer Lawton (Johns Hopkins Medicine, Baltimore, USA) addressed evidence and surgical challenges for multiple arterial CABG in women.
“Women have a higher risk of mortality with coronary bypass grafting compared to men,” Lawton commented, adding that this has been shown “time and again” in retrospective and propensity matched studies. “It is multifactorial, as Dr Sandner mentioned, probably related to knowledge of clinicians, also patient factors, and the fact that women tend to present for surgery about ten years older and with multiple comorbidities.”
Turning to the question of how to improve mortality in women undergoing coronary surgery, Lawton pointed to a study led by Stephen Fremes (Sunnybrook Health Sciences Centre, Toronto, Canada), published in Heart in 2020, in which it was shown that women who received multiple arterial grafts had improved long-term survival over a ten-year period and a higher rate of freedom from major adverse cardiovascular events. A further propensity matched meta-analysis, conducted by Gaudino and colleagues, also found a higher survival probability in women that received multiple arterial grafts.
“This is something that we as surgeons can do,” Lawton said, in reference to the adoption of multiple arterial grafting among female patients, something that appears to be currently underutilised.
Lawton also highlighted the findings from the analysis of the Society of Thoracic Surgeons (STS) database, first shared in 2021, containing procedural data from more than 1.2 million patients, showing that women were 14–22% less likely to undergo revascularisation strategies including grafting of the left internal mammary artery (LIMA) to the left anterior descending (LAD) artery, complete revascularisation, or multiarterial grafting.
Lawton suggested a number of potential strategies to encourage adoption of multiarterial grafting, including better training in these techniques or embedding the use of a second arterial graft within quality metrics.
She ended with a quote from Maya Angelou, summing up the need for more evidence in this arena. “Do the best you can until you know better, then when you know better, do better.”
ROMA Women
If studies focusing on CABG outcomes in women have been lacking to date, one trial is looking to begin the process of bridging this gap. 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.
Gaudino followed Lawton’s presentation by offering an update on the trial’s progress to date. “Even though the evidence is limited, there is reason to believe that multiple arterial grafting may be beneficial in the general CABG population, but even more so in women undergoing bypass surgery,” Gaudino commented.
“This is exactly the reason why I believe a randomised trial of multiple arterial grafting in women is necessary. Contrary to what we have traditionally believed, we have no evidence that multiple arterial grafting is better—we will find out in a couple of years—but one reasonable option is that the treatment effect is different by sex.”
The ROMA trial, which had a majority male population, completed enrolment with over 4,000 patients and is expected to report its first outcomes in 2026. Enrolment has remained open solely for female patients, with a further 1,310 expected to be included alongside the 690 recruited in the main ROMA trial. At the time of his presentation, Gaudino noted that a total of 273 female patients had been enrolled in ROMA Women, with a “better than expected” rate of recruitment in its first few months. “If we can keep this pace we can make this impossible trial possible even faster than we thought,” he said.
The final speaker in the session, Rashmi Yadav (Royal Brompton & Harefield Hospitals, London, UK), reminded attendees that the “data gap” between women and men extends far beyond coronary surgery. “Although cardiovascular disease causes one third of deaths in all women, it is understudied, underrecognised, undertreated and women are underrepresented in clinical trials,” she said.
Yadav highlighted that there are some technical, anatomical differences between men and women that can pose challenges for surgeons, as well as what she described as “non-technical, unquantifiable” challenges.
“There is evidence that women are more perceptive of a non-empathetic physician. Compared to a male patient, a women is more likely to be affected by the manner of her surgeon,” Yadav commented. “That brings me to the thorny question of whether it matters that there is sex concordance between the surgeon and the patient and does it matter for postoperative outcomes?”
In answer to this question, Yadav commented that in her view, it did not matter for the vast majority of patients, “but every once in a while you will come across a patient where it matters to them whether their surgeon is a woman or not”.
