Sex differences in computed tomography-derived fractional flow reserve-guided management of stable coronary artery disease: a subgroup analysis of the TARGET trial.
Ding Y, Liu Z, et al. • EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology • 2026
CT-FFR-guided management was associated with different clinical patterns between females and males, with a lower 2-year adverse event rate observed among females in the CT-FFR group, though the absence of a statistically significant interaction between sex and treatment strategy means these findings should be considered exploratory and hypothesis-generating.
Key Findings
Results
Female patients in this stable CAD cohort were significantly older than males but had comparable anatomical CAD severity.
Females were older than males (62.3±8.1 years vs 58.2±10.7 years; p<0.001)
Despite the age difference, anatomical CAD severity was described as comparable between sexes
The study included 1,216 patients with 30-90% coronary stenosis on CCTA randomised to CT-FFR-guided care or standard care
This was a post hoc subanalysis of the randomised TARGET trial (ClinicalTrials.gov: NCT03901326)
Results
CT-FFR-guided care significantly reduced ICA without obstructive CAD and increased early revascularisation in males but not in females.
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 sex-specific impact on the primary endpoint differed between males and females
CT-FFR guidance reduced unnecessary angiography particularly in males
No significant primary endpoint benefit was observed in females under CT-FFR-guided care
Results
CT-FFR-guided management was associated with a significantly lower 2-year MACE rate in females compared with standard care.
Adjusted hazard ratio for MACE in females: HR 0.48, 95% CI: 0.27-0.87; p=0.015
The secondary endpoint was major adverse cardiovascular events (MACE) at 2 years
No significant difference in 2-year MACE was observed in males (adjusted HR 0.89, 95% CI: 0.59-1.33; p=0.574)
Females with standard care had a higher MACE rate compared to females in the CT-FFR group over 2 years
Discussion
The interaction between sex and treatment strategy was not statistically significant, rendering the sex-specific findings exploratory and hypothesis-generating.
The authors explicitly stated: 'given the absence of a statistically significant interaction between sex and treatment strategy, these findings should be considered exploratory and hypothesis-generating'
This was a post hoc subgroup analysis, which limits causal inference
The differential MACE benefit seen in females versus males cannot be definitively attributed to a true sex-treatment interaction based on this analysis
Background
Females with stable CAD often present with less obstructive disease on invasive coronary angiography yet experience worse outcomes than males.
This sex paradox was cited as motivation for the study
CT-FFR improves physiological assessment of coronary lesions beyond CCTA alone
The sex-specific clinical impact of CT-FFR guidance was described as 'uncertain' prior to this analysis
The study population included patients with 30-90% coronary stenosis on CCTA, a range that encompasses both obstructive and non-obstructive lesions
What This Means
This research examined whether a non-invasive imaging technology called CT-FFR (computed tomography-derived fractional flow reserve) — which measures blood flow through coronary arteries using CT scans — works differently in women versus men with stable coronary artery disease. The study analyzed data from 1,216 patients in a randomized trial, comparing CT-FFR-guided care to standard care. Women in the study were older on average than men (62 vs. 58 years) but had similar degrees of artery narrowing. The researchers found that CT-FFR guidance helped men primarily by reducing unnecessary invasive procedures — specifically, it reduced cases where men underwent invasive angiography only to find no significant blockages. For women, however, CT-FFR guidance appeared to offer a different benefit: over two years, women receiving CT-FFR-guided care had about half the rate of major adverse cardiovascular events (such as heart attacks) compared to women receiving standard care.
This research suggests that CT-FFR guidance may benefit women and men in different ways — reducing unnecessary procedures in men while potentially improving long-term cardiovascular outcomes in women. However, the authors caution that because this was a post hoc (after-the-fact) subgroup analysis and the statistical test for whether sex truly modified the treatment effect did not reach significance, these results should be treated as preliminary and hypothesis-generating rather than definitive conclusions. The finding is notable given the well-known paradox that women with stable coronary artery disease often show less severe blockages on invasive testing yet tend to have worse outcomes than men, suggesting that physiological assessment tools like CT-FFR may be particularly valuable in this group. Further dedicated studies in women would be needed to confirm these findings.
Ding Y, Liu Z, Shan D, Wang X, Guo Z, Xin R, et al.. (2026). Sex differences in computed tomography-derived fractional flow reserve-guided management of stable coronary artery disease: a subgroup analysis of the TARGET trial.. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. https://doi.org/10.4244/EIJ-D-25-01383