CT-FFR in stable chest pain: different patterns by sex, and no interaction to prove it

Design

Post hoc sex-stratified subanalysis of the randomised TARGET trial

Population

1,216 patients with stable coronary artery disease and 30% to 90% stenosis on CT coronary angiography

Primary outcome

Invasive angiography without obstructive disease, or no intervention despite obstructive disease, within 90 days; two-year major adverse cardiovascular events as secondary

Effect

Two-year MACE adjusted HR 0.48 (95% CI 0.27 to 0.87) in women and 0.89 (0.59 to 1.33) in men; no significant sex-by-treatment interaction

TARGET randomised 1,216 patients with 30% to 90% stenosis on CT coronary angiography to onsite CT-derived fractional flow reserve guidance or standard care. This post hoc analysis splits the trial by sex. Women were older, 62.3 ± 8.1 years against 58.2 ± 10.7, with comparable anatomical severity. CT-FFR guidance reduced invasive angiography that found no obstructive disease, and increased early revascularisation, in men but not in women. Over two years, major adverse cardiovascular events were lower with CT-FFR guidance among women, adjusted HR 0.48 (95% CI 0.27 to 0.87, p = 0.015), and not among men, adjusted HR 0.89 (0.59 to 1.33, p = 0.574).

The authors state plainly that there was no significant interaction between sex and treatment strategy, and that the findings are exploratory. That caveat carries the weight of the whole analysis. A significant result in one subgroup and a null in another is the most common way a subgroup analysis misleads: unless the difference between the two is itself significant, the honest reading is that the trial did not show the effect varies by sex.

What is worth carrying into practice is the older, better-supported point the analysis restates. Women with stable chest pain more often have symptoms with less obstructive disease on angiography and worse outcomes, and physiological assessment on the CT rather than anatomical stenosis alone is a reasonable response to that mismatch. Use CT-FFR where it is available for the reason the main trial supports — fewer invasive angiograms that find nothing — and do not tell a woman that it lowers her risk of events, which this analysis is not able to show.

• Apply the main trial result: CT-FFR reduces invasive angiography that finds no obstructive disease.
• Do not present the female MACE result as a sex-specific benefit; there was no significant interaction.
• Anatomical stenosis alone under-describes ischaemia more often in women — that point predates this analysis.
• Onsite CT-FFR is the version tested; results do not automatically transfer to core-lab or offsite services.
• Where CT-FFR is unavailable, the decision reverts to stenosis severity and symptoms, not to this subgroup.

The statistics, in plain English

The two hazard ratios, 0.48 in women and 0.89 in men, look like different answers, but the test of whether they truly differ is the interaction term — and it was not significant. Comparing p-values across subgroups instead of testing the interaction is the classic error, and it produces apparent sex differences reliably in trials that have none. There is also a second problem: with the trial split in two, each half is powered for less than the whole, so the female interval, 0.27 to 0.87, is wide and its lower bound implausibly large for a diagnostic strategy. Post hoc subgroup findings of this shape are worth a prospective test, not a change of practice.

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