Medication equity and sex differences in the CT-FFR guided management of patients with stable coronary artery disease: from the TARGET randomized trial

Background Women with stable coronary artery disease (CAD) often exhibit distinct clinical profiles from men, including a lower likelihood of obstructive CAD on invasive coronary angiography (ICA) but worse cardiovascular outcomes. Coronary computed tomography-derived fractional flow reserve (CT-FFR) enhances diagnostic accuracy beyond anatomical assessment with CCTA, yet its impact on sex-specific differences in patient management remains unclear. Purpose This study aimed to evaluate the impact of a CT-FFR-guided strategy on clinical decision-making and outcomes in women and men. Methods The Effect of On-site CT-derived Fractional Flow Reserve on the Management of Decision Making for Patients with Stable Chest Pain (TARGET) trial was a randomized control trial examining the on-site CT-FFR pathway versus standard care in patients with stable CAD. A total of 1,216 patients with a stenosis of 30% to 90% on CCTA were enrolled in 6 medical centers. The primary endpoint was the proportion of patients undergoing ICA without obstructive CAD or with obstructive CAD who did not undergo intervention within 90 days. Secondary endpoints included major adverse cardiovascular events (MACE) and medication at 1-year follow-up. Results Women were generally older (62.3 ± 8.1 years vs 58.2 ±10.7 years, P<0.001) and had a lower prevalence of current smoker and alcohol usage. The prevalence of other risk factors such as hypertension, dyslipidemia, diabetes mellitus, and family history of CAD was comparable in women and men. In the CT-FFR care group, 141 (67.1%) women and 280 (70.4%) men underwent ICA, compared to 173 (78.3%) women and 310 (80.1%) men in the standard care group. Compared to standard care, men in the CT-FFR care group had a significantly lower rate of ICA without obstructive CAD or with obstructive CAD but without intervention (51.9% vs. 26.8%, P<0.001). In contrast, this reduction was not significant for women (35.8% vs. 31.2%, P=0.388). At the 1-year follow-up, revascularization rates increased significantly in men within the CT-FFR care group (52.8% vs. 40.3%, P<0.001) but not in women (47.2% vs. 54.5%, P=0.137). Notably, late revascularization (>90 days) was significantly reduced in women receiving CT-FFR guidance (1.0% vs. 4.1%, P=0.040). However, overall MACE at 1 year did not differ between sexes in either group (Log-rank P=0.656). Additionally, the CT-FFR care group exhibited a reduction in sex-based disparities in medication usage compared to standard care. Conclusion CT-FFR demonstrates sex-specific effects on patient management, reducing unnecessary ICA and increasing revascularization in men but not in women. The reduction in late revascularization in women may be linked to improved medication equity in the CT-FFR group. However, these changes did not translate into significant differences in 1-year MACE between sexes.Sex differences in the primary outcome Disparity of medication between sexes