Multiple Arterial CABG Benefits Both Sexes, but Risk Cutoffs Vary

Multiple arterial grafting (MAG) leads to better CABG outcomes compared with single arterial grafts (SAG) in patients with low, but not high, preoperative risk, according to a new analysis. However, these risk cutoffs differ between men and women, leading the researchers to argue the need for dedicated surgical studies in women.

“I hope that this work [will] be a wake-up call for the surgical community so that my colleagues understand that we need to study women in studies that are designed specifically for women,” lead author Mario Gaudino, MD (Weill Cornell Medicine, New York, NY), told TCTMD. “We have to stop assuming that what we see in the general population is true for women. It is not the case.”

Plenty of recent studies have demonstrated the widespread benefit of MAG over saphenous vein grafting in CABG, but surgeons still don’t seem to be enthusiastically performing this technique because of habit or technical difficulty.

For the current study, published yesterday in JAMA Cardiology, Gaudino and colleagues included 63,402 patients (76% men) from New York’s Cardiac Surgery Reporting System who underwent nonemergent CABG with multiple grafts and at least one arterial conduit between 2005 and 2014. Unsurprisingly, women had a higher preoperative comorbidity burden.

We have to stop assuming that what we see in the general population is true for women. It is not the case. Mario Gaudino

Among 9,512 male and 1,860 female propensity-matched pairs, 7-year mortality was lower for men who received MAG vs SAG (adjusted HR 0.80; 95% CI 0.73-0.87) but not women (adjusted HR 0.99; 95% CI 0.84-1.15). The same relationship was seen for repeat revascularization, MACE, and MACCE, but no difference in stroke was seen in either sex. The risk of acute MI was lower following MAG vs SAG for both men and women at 7 years.

Also, while 7-year mortality was lower for both low-risk males (8.6% vs 11.1%; adjusted HR 0.80; 95% CI 0.73-0.89) and females (13.0% vs 16.3%; adjusted HR 0.80; 95% CI 0.65-0.97) who received MAG versus SAG, it was similar for high-risk individuals of either sex. However, in an analysis using different low-risk cutoffs for males and females, MAG was associated with lower mortality in all low-risk males but only in women with a risk score lower than 11 (corresponding to a 1-year mortality of 17.5%).

A fully adjusted analysis, including the risk score, showed that while MAG was inversely linked with mortality (adjusted HR 0.53; 95% CI 0.46-0.61), female sex (adjusted HR 1.44; 95% CI 1.26-1.64) and the risk score (adjusted HR 1.28; 95% CI 1.27-1.29) were positively associated.

Missing Information

The differences in the effect of MAG between males and females is likely mostly explained by the higher baseline risk profile of the latter, Gaudino said. “But even when you stratify by risk profile, there is a difference. . . . So, what this is telling me is that there is a difference that we are not able to identify based on this data set.”

The researchers were unable to access information about the quality of the coronary vessels and bypass grafts, but the biology of the disease is also different among men and women, he explained. “It's also possible there is a technical factor. Women have smaller coronary arteries, smaller conduits, so maybe the operation is more challenging in women and maybe the technical complexity is different, and this is why we see different results. Unfortunately, this analysis opens more questions than provides answers.”

Although Gaudino is leading ROMA, the largest trial yet to compare the use of single versus multiple arterial graft CABG, he acknowledges that only 20% of the 4,000 participants will be female—not enough to truly draw conclusions from. “My next project is to leverage ROMA to then perform a separate trial which will be in women only. So we can use the same risk factors, trial network, but then finally design a trial only in women that has never been done before,” he said. “It's very challenging because of the relative rarity of women [and] recruitment is also much more challenging, but I think it is the moment that we need to do that.”

At the moment, there is no evidence from large randomized trials to say that MAG is more beneficial in either sex, but Gaudino argued that its use needs to increase across the board.

“When you look at the results of the study defined by score, low-risk women like low-risk men derive benefit even in terms of survival with the use of multiple arterial grafting. So yes, definitely, multiple arterial grafting should be used in women, and should be used more frequently than actually they are being used.”

Patients with longer life expectancies in particular “deserve the use of multiple arterial grafting, but this is true for men and women, not only for women,” he added.