Compared with men, women continue to have a roughly 30-40% higher risk of dying following coronary artery bypass surgery, according to a large study led by investigators at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.

The analysis showed that, without adjusting for differences in age and other health factors that influence risk, the female bypass patients had a 2.8%rate of death during or soon after surgery, compared with 1.7% for male patients, a nearly 50% difference that only dropped 10-20% after accounting for these factors.

The study, which appears Mar. 1 in JAMA Surgery, was based on data from nearly 1.3 million bypass surgeries performed in the United States from 2011 to 2020. It confirms the findings of studies based on surgery data from prior decades.

“This should be a ‘wake-up call’ for cardiothoracic surgeons – women still have a higher risk of adverse outcomes following coronary artery bypass surgery, and there doesn’t seem to have been any change in this trend over the past decade,” said study lead investigator Dr. Mario Gaudino, the Stephen and Suzanne Weiss Professor in Cardiothoracic Surgery at Weill Cornell Medicine and a cardiothoracic surgeon at NewYork-Presbyterian/Weill Cornell Medical Center.

Doctors perform about 370,000 coronary artery bypass graft surgeries in the U.S. every year. Over the past few decades, advances in surgical techniques and overall care have brought improved outcomes from these surgeries.

However, since the 1990s, studies of these surgeries have been finding evidence that, compared with male patients, female patients tend to have worse outcomes. Female bypass surgery patients on average are older and more likely to have chronic diseases such as diabetes and hypertension. But even when researchers adjust their analyses to take these factors into account, women still appear to have worse outcomes on average.

One of the big questions for the field has been whether these sex differences in outcomes, first observed more than 30 years ago, have continued in recent years as surgical techniques and surrounding care have improved. To answer this question, Gaudino and colleagues – including surgeons in the U.S., Canada, and Austria—analyzed bypass surgery cases from 2011-20 in the Adult Cardiac Surgery Database, which is maintained by the Chicago-based Society for Thoracic Surgeons. The database covers a large proportion of U.S. bypass surgeries, and also includes data from medical centers abroad.

The analysis included a total of 1,297,204 bypass surgeries, of which 317,716 were in women. The main outcome measures were “operative mortality” – death during surgery or within the 30 days following surgery—and a composite measure defined as operative mortality or a major post-operative complication, such as stroke or kidney failure.

Without adjusting for differences in age and other health factors that influence risk, the investigators found that female bypass patients had a 2.8% rate of death during or soon after surgery, compared with 1.7% for male patients; and a 22.9% rate of the composite measure compared with 16.7% for male patients. Even after adjustment for male/female differences in those risk factors, being female appeared to bring a significantly higher risk of death or major complications.

For mortality, being female was associated with a 28% to 41% higher risk depending on the year of surgery during the covered period. For the combined outcome measure, being female was associated with a 2% to 9% higher risk. There was no significant trend for either measure during the analyzed period.

The findings underscore the importance of determining why women have worse outcomes for this relatively common surgery, said Gaudino, who is also director of the Joint Clinical Trials Office at Weill Cornell Medicine and NewYork-Presbyterian.

“We’re clearly missing something here, and that means we need more data on women – data on the physiology of their coronary artery disease and how it tends to differ from men’s, and data on their responses to different treatments and surgical techniques,” he said.

To that end, he and his colleagues are planning a clinical trial exclusively in female patients, to see if the use of multiple coronary artery bypasses during surgery improves outcomes over single-artery bypasses.

Jim Schnabel is a freelance writer for Weill Cornell Medicine.