“I have known that women have had worse outcomes following CABG since I was a medical student 30 years ago,” says Mario Gaudino, MD, PhD, a cardiothoracic surgeon at NewYork-Presbyterian/
Dr. Mario Gaudino
Cardiac surgeons perform some 370,000 coronary artery bypass graft (CABG) surgeries in the United States every year. While advances in surgical techniques and overall care during the past few decades have resulted in improved CABG outcomes, studies throughout this period continued to demonstrate that women tend to have worse outcomes compared to men. The challenge in validating CABG outcomes specific to women, in part, relates to the higher percentage of men undergoing CABG.
“In general, studies related to CABG include 80 percent men to 20 percent women,” notes Dr. Gaudino. “Clearly, we should accept the fact that what we see in men may not be applicable, and probably is not applicable, to women. Coronary artery disease presents differently in women. They have more microvascular dysfunction and more spasm so the indication for coronary revascularization may actually be different between men and women. Women have smaller body size and are generally more anemic when they get to surgery. These two factors together make intraoperative hemodilution much more concerning for women.”
To address this issue, Dr. Gaudino and surgical colleagues in the U.S., Canada, and Austria sought to determine if operative outcomes in women undergoing CABG improved from 2011 to 2020. The researchers undertook a study to analyze bypass surgery cases from this time period drawing on the Adult Cardiac Surgery Database maintained by the Society for Thoracic Surgeons. The database covers a large proportion of U.S. bypass surgeries and also includes data from medical centers abroad. Their analysis included 1,297,204 bypass surgeries of which 317,716 (24.5 percent) were in women. The main outcome measures were operative mortality and a composite measure defined as operative mortality or a major postoperative complication, such as stroke or kidney failure.
The study’s findings, published in the March 1, 2023, issue of JAMA Surgery, confirmed the findings of studies based on surgery data from prior decades – women undergoing CABG still had a higher operative mortality and incidence of the composite of operative mortality and morbidity compared with men and there was no improvement during the 10-year study period. Specifically, the investigators showed:
- Without adjusting for differences in age and other health factors that influence risk, the female bypass patients had a 2.8 percent rate of death during or soon after surgery, compared with 1.7 percent for male patients; and a 22.9 percent rate of the composite measure compared with 16.7 percent for male patients
- After adjusting for male/female differences in risk factors, females continued to have a significantly higher risk of death or major complications
- Being female was associated with a 28 to 41 percent higher risk for mortality depending on the year of surgery during the study period, and was associated with a two to nine percent higher risk for the combined outcome measure
“Women still having a higher risk of adverse outcomes following coronary artery bypass surgery should be a wake-up call for cardiothoracic surgeons,” says Dr. Gaudino, the study’s lead investigator. “The findings underscore the importance of determining why women have worse outcomes for this relatively common surgery. We’re clearly missing something here, and that means we need more data on physiology of female coronary artery disease, how it differs from men’s, and their responses to different treatments and surgical techniques. In order to make meaningful changes to the procedure, I would make the bold choice to conduct a study exclusively on women. This is a 180-degree change that we need to make in order to better inform our practice.”
When in ROMA...
Dr. Gaudino’s recommendation is coming to fruition with the very recent launch in March 2023 of ROMA: Women, a spinoff study of the ROMA (Randomization of Single vs Multiple Arterial Grafts) trial. The first ROMA study is evaluating if the use of two or more arterial grafts compared to a single arterial graft is associated with improved survival. The study enrolled approximately 4,300 men and women from over 100 sites in North America, Europe, Asia, South America, and Australia.
“The use of arterial grafts has been found in some studies to be more beneficial in women compared to men,” says Dr. Gaudino. “We will compare the results of using single versus multiple arterial grafts in ROMA:Women, the first randomized trial dedicated to women.”
ROMA: Women will not only leverage the infrastructure and the participating sites of the first ROMA trial, the investigators are also using a statistical approach that allows women who are included in ROMA to also be included in ROMA: Women. “We would like to enroll 2,000 women in the ROMA: Women trial. We are tapping into over 600 women enrolled in ROMA. So, we need only 1,300 women to complete our study cohort,” says Dr. Gaudino. “Having said that, even 1,300 is a huge number because, again, women represent a minority of patients referred for bypass surgery. We are expecting to double the number of participating sites over the 100+ involved in the original ROMA trial to reach our enrollment goal. We welcome additional collaborators with any interest in the trial in any capacity.”
Dr. Gaudino serves as lead investigator for both ROMA, which just completed enrollment with results expected by late 2025, and ROMA: Women, which enrolled its first patient in March 2023 and is expected to conclude in 2028-2029.
The ROMA: Women trial already has received overwhelming encouragement from professional societies, patient organizations, and surgeons, and endorsement from the Global Cardiovascular Research Funders Forum and is exploring funding options.
