Long-term prognostic significance of negative CT-derived fractional flow reserve in patients with stable CAD: A meta-analysis of reconstructed time-to-event data

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) is an emerging tool allowing for noninvasive physiological assessment and risk stratification of patients with coronary artery disease (CAD). However, the long-term prognostic impact of negative CT-FFR (CT-FFR >0.80) in patients with stable CAD requires further investigation. METHODS: In this systematic review and meta-analysis, a comprehensive search was conducted across PubMed, Embase, Web of Science, and Scopus to identify studies comparing clinical outcomes in patients with stable CAD and CT-FFR >0.80 or ≤0.80, published up to October 15, 2025. Individual patient data were reconstructed by processing the extracted time points, survival probabilities, and the number of patients at risk from Kaplan-Meier curves. The pooled survival curves and Cox proportional hazard model were fitted to estimate HRs and 95% CIs. The restricted mean survival time (RMST) was also calculated as the area under the survival curve for each group. RESULTS: Of the 17 included studies, 15 comprising 14,315 patients were used in the IPD-reconstructed meta-analysis of incident Major adverse cardiovascular events (MACE) or a composite of all-cause mortality and non-fatal MI. Over a follow-up period of up to 120 months, CT-FFR ≤0.80 was associated with a 197% increased risk of MACE compared to those with CT-FFR >0.80 (HR: 2.97; 95% CI: 2.54-3.48; p ​< ​0.001). The 10-year MACE-free survival rate was 77.1% in the CT-FFR ≤0.80 group versus 91.4% in the CT-FFR >0.80 group. RMST analysis revealed that over this period, Patients with CT-FFR >0.80 had a mean MACE-free survival of 114.1 months, compared to 94.8 months in those with CT-FFR ≤0.80 (p ​< ​0.001). CONCLUSION: Patients with stable CAD and CT-FFR >80 can be safely deferred from invasive evaluations in the absence of other indications, due to their high rates of long-term MACE-free survival.