Sex differences in computed tomography-derived fractional flow reserve-guided management of stable coronary artery disease: a subgroup analysis of the TARGET trial.

Females with stable coronary artery disease (CAD) often present with less obstructive disease on invasive coronary angiography (ICA) yet experience worse outcomes than males. Coronary computed tomography-derived fractional flow reserve (CT-FFR) guidance improves the physiological assessment of coronary lesions beyond coronary computed tomography angiography (CCTA), but its sex-specific clinical impact remains uncertain. This study aimed to investigate sex-based differences in treatment and clinical outcomes between CT-FFR-guided and standard care strategies in patients with stable CAD. In this post hoc subanalysis of the randomised TARGET trial, 1,216 patients with 30-90% coronary stenosis on CCTA were randomised to onsite CT-FFR-guided care or standard care. The primary endpoint was the proportion of patients who underwent ICA without obstructive CAD or had no intervention despite obstructive CAD on ICA within 90 days of CCTA. The secondary endpoint was major adverse cardiovascular events (MACE) at 2 years. Females were older than males (62.3±8.1 years vs 58.2±10.7 years; p<0.001) but had comparable anatomical CAD severity. CT-FFR-guided care significantly reduced ICA without obstructive CAD and increased early revascularisation in males but not in females. Over 2 years, CT-FFR-guided management was associated with a significantly lower MACE rate in females compared with standard care (adjusted hazard ratio [HR] 0.48, 95% confidence interval [CI]: 0.27-0.87; p=0.015), whereas no significant difference was observed in males (adjusted HR 0.89, 95% CI: 0.59-1.33; p=0.574). CT-FFR-guided management was associated with different clinical patterns between females and males. Particularly in males, CT-FFR guidance reduced unnecessary angiography. A lower 2-year adverse event rate was observed among females in the CT-FFR group. However, given the absence of a statistically significant interaction between sex and treatment strategy, these findings should be considered exploratory and hypothesis-generating. (ClinicalTrials.gov: NCT03901326).