Graft failure during coronary artery bypass graft (CABG) surgery is more frequent in women, according to a new study, which links the complication to a higher risk of adverse cardiac events and death post-surgery. In the study, researchers found that graft failure was significantly more frequent in women than men. The failure was associated with an increased risk of myocardial infarction, repeat revascularization, and death. However, the paper, which was published Monday online, questions whether the differences in CABG outcomes between sexes was related to higher rates of graft failure in women. “The present analysis, however, suggests that this is not the case, because our data showed that graft failure did not mediate the excess risk of death associated with female sex,” said the authors, led by Sigrid Sandner, MD from Weill Cornell Medicine in New York. “This highlights the need to address other disparities in the diagnosis and treatment of coronary disease in women to reduce the gap in CABG outcomes between sexes.” Pooled patient data The investigation, which was also published in the July 9 issue of the Journal of the American College of Cardiology, looked at pooled individual patient data from seven randomized clinical trials (n=4,413, of whom 777 were women). Results from a median imaging follow-up of 1.03 years revealed that graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level (P=0.02) and 20.5% vs 15.8% at the graft level (P<0.001). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (odds ratio [OR]: 3.94; 95% confidence interval [CI]: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, hazard ratio [HR]: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). “The higher rate of graft failure in women relative to men was particularly evident for the RITA [right internal thoracic artery],” the paper’s authors said. “The ITA has a smaller diameter and is more prone to spasm in women, potentially making the use of the RITA technically more challenging and more likely to fail in women.” Smoking as risk factor The paper also highlights the risk of graft failure as significantly increased among women who were smokers. The researchers explained that smoking reduces flow-mediated vascular dilatation, which is considered the earliest marker of atherogenesis and vascular dysfunction. “The higher risk in women appears biologically plausible as susceptibility to oxidative stress and subsequent endothelial dysfunction is greater in women, particularly postmenopausal women,” they added. Further study needed Amy A. Sarma, MD, from Massachusetts General Hospital in Boston, and Jared A. Spitz, MD, from Inova Schar Heart and Vascular in Fairfax, Virginia, echoed the need for further study of the impact of small-diameter vessels, increased vessel spasm risk and endothelial dysfunction on increasing graft failure risk. Delving deeper in their accompanying editorial comment, the experts highlighted that failure rates were highest for venous grafts (23.6%) and lowest for the left internal thoracic artery and radial artery grafts. They also noted a higher incidence for the RITA, although they added: “This should be interpreted with caution given the overall low numbers in this study (33 grafts).” Women underrepresented Concluding their editorial, Sarma and Spitz said optimal surgical revascularization strategies among women are yet to be understood, largely because of the underrepresentation of women in cardiovascular trials. In addition, it also remains unclear why women are less likely to undergo complete surgical revascularization and to receive arterial conduits. “However, the authors’ finding that graft failure itself does not appear to mediate increased risk among women suggests instead that graft failure acts more like a marker of increased risk,” the editorialists wrote. “This is not surprising when considering the multitude of sex differences in risk factors and disparities in preventive medical treatment among women. Looking ahead, the commenters added: “However, it is time to move beyond simply describing these disparities and develop evidence-based strategies for ensuring delivery of optimal preventive therapy, improving enrollment and engagement with cardiac rehabilitation programs, and better understanding nonatherosclerotic contributors to risk among women, including endothelial dysfunction.” Study setup Seven randomized clinical trials (n=4,413, 777 women) were included, where a pooled analysis of individual patient data with systematic imaging follow-up was then performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging and death after imaging. Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. For assessment of the association of graft failure with adverse cardiac events, the primary outcome was the incidence of the composite of myocardial infarction (MI) or repeat revascularization between CABG and graft imaging. Sources: Sandner S, Redfors B, An KR, et al. Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications. J Am Coll Cardiol. 2024;84:182–191. Sarma AA, Spitz JA. Sex Differences, Graft Failure, and Mortality: An Ounce of Prevention After the Pound of Cure. J Am Coll Cardiol. 2024;84:192–194. Image Credit: Fatih – stock.adobe.com