Women with 3-vessel coronary artery disease (3VD) have similar outcomes to men following placement of a drug-eluting stent (DES) using percutaneous coronary intervention (PCI) but fare worse with coronary artery bypass grafting (CABG). This begs an important question: Should sex play a role in deciding revascularization strategy in 3VD? This was the summary of the analyzed by Stanford University’s Kuniaki Takahashi, MD, PhD, and Hisao Otsuki, MD, PhD, following a prespecified subgroup analysis of the 1,500-patient FAME 3 trial at 3 years. The findings were published online in JACC: Cardiovascular Interventions. The investigator-initiated FAME 3 trial is the first randomized control study to compare FFR-guided PCI with current-generation DES with CABG in 3VD patients, the researchers noted. The trial did not meet the prespecified noninferiority primary endpoint for PCI regarding major adverse cardiac or cerebrovascular events (MACCE) at 1 year. Nor was any significant difference observed between the two revascularization modalities at 3 years for the key secondary endpoint, a composite of death, myocardial infarction (MI) or stroke. The current analysis set out to identify any differences in outcomes between the 265 women and 1,235 men included in the study. Overall, 757 patients were randomized to FFR-guided PCI and 743 to CABG. Of these, the PCI arm included 141 women and 616 men, and the CABG arm included 124 women and 619 men. At baseline, overall, women were older (a mean of 67.4 years versus 64.6 years), more frequently had hypertension (78.1% versus 72%) and a family history of coronary artery disease (CAD: 35.8% versus 29.6%) and were less frequently smokers (16.6% versus 19.2%). Women in the study also had fewer lesions (a mean of 4.1 ± 1.2 versus 4.3 ± 1.3; P = 0.008) and less complex CAD as represented by the anatomical SYNTAX score. In the PCI arm, women at baseline had a a lower mean functional SYNTAX score (a mean of 21.0 ± 9.5 vs 23.1 ± 8.2; P = 0.007) with a lower proportion of a high (≥23) functional SYNTAX score (39.0% vs 52.4%; P = 0.004), resulting in less stenting for women with a shorter total stent length per patient. In the CABG group, women had higher perioperative surgical risks as assessed by the STS score and EuroSCORE II (mean of 1.7 ± 1.4 versus 1.1 ± 0.8; P < 0.001), though received fewer arterial grafts (mean of 1.1 ± 0.5 versus 1.3 ± 0.5; P <0.001), a lower percentage of left internal mammary artery grafts (93.3% vs 97.8%; P = 0.007) and a lower percentage of multiple arterial grafts (12.0% vs 27.0%; P = 0.001). Off-pump surgery was also more frequently performed in women in the CABG group compared with men (34.8% vs 22.0%; P = 0.003). At 3 years, women had a significantly higher risk of MACCE — a composite of composite of all-cause death, MI, stroke or repeat revascularization — at 3 years, than men following CABG (18.1% vs 11.7%; adjusted hazard ratio [HR]: 2.07; 95% confidence interval [CI]: 1.19-3.60; P = 0.010). However, in the PCI group, after adjustment for baseline imbalances between sexes, women and men fared similarly at 3 years (18.2% vs 19.1%; adjusted HR: 1.27; 95% CI: 0.79-2.03; P =0.324). Treatment effects by sex The researchers went on to compare PCI and CABG groups for the same sex. Women undergoing PCI had a similar risk of MACCE at 3 years compared with CABG (adjusted HR: 1.15; 95% CI: 0.62-2.11; P = 0.662), while men undergoing PCI had a higher risk of MACCE at 3 years compared with CABG (adjusted HR: 1.68; 95% CI: 1.25-2.25; P for interaction = 0.142). The effect for men was mainly driven by a higher risk of myocardial infarction (adjusted HR: 2.11; 95% CI: 1.26-3.56; P for interaction = 0.102) and repeat revascularization (adjusted HR: 2.26; 95% CI: 1.47-3.47; P for interaction = 0.071). “Women have similar outcomes after FFR-guided PCI compared with CABG, while men have better outcomes with CABG, although the interaction term did not reach statistical significance,” the authors wrote. They went on to call for longer-term follow-up to see whether these sex-related differences in outcomes persist, and whether being female should be taken into account when determining 3VD revascularization strategy using contemporary techniques. Smaller coronary arteries In an accompanying editorial, Enrico Fabris, MD, PhD, from the University of Trieste, Italy, and Roxana Mehran, MD, from Icahn School of Medicine at Mount Sinai, New York, said the findings highlight the “significant concern” from trials and registries that women have worse outcomes than men after CABG. “This worse outcome in women is likely multifactorial; however, it is known that women have smaller coronary arteries than men, which can increase the technical challenges of CABG surgery and potentially account for incomplete revascularization, which may contribute to the higher complication rates,” they said. The editorialists stressed that there is a “crucial” need to reassess strategies for treating women, and to address the “many unknowns” remaining regarding the differences in outcomes between the sexes which “may translate in personalized approaches for coronary revascularization.” Sources: Takahashi K, Otsuki H, Zimmermann F, et al. Sex Differences in Patients Undergoing FFR-Guided PCI or CABG in the FAME 3 Trial. JACC: Cardiovasc Interv 2024; DOI: 10.1016/j.jcin.2024.09.030. Fabris E, Mehran R. Personalized Revascularization Strategies: Should Sex Shape PCI vs CABG Choices? JACC: Cardiovasc Interv 2024; DOI: 10.1016/j.jcin.2024.10.042. Image Credit: Mirko Vitali – stock.adobe.com