Clinical outcomes of angiography-derived fractional flow reserve compared with invasive and imaging-guided PCI: a network meta-analysis

Background Wire-free angiography-derived fractional flow reserve (FFR) has emerged as an alternative physiological approach for guiding percutaneous coronary intervention (PCI). However, direct comparative evidence against established strategies, including angiography-guided, wire-based FFR-guided, and intravascular ultrasound (IVUS)-guided PCI, remains limited. Purpose To compare the clinical effectiveness of angiography-derived FFR guidance with other established coronary assessment strategies using a frequentist network meta-analysis. Methods A systematic search identified randomised controlled trials comparing angiography-derived FFR-guided PCI with angiography-, wire-based FFR-, or IVUS-guided strategies. Outcomes included major adverse cardiovascular events (MACE), cardiovascular death, myocardial infarction (MI), and ischaemia-driven target vessel revascularisation (ID-TVR). A random-effects frequentist network meta-analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). P-scores were used to rank treatment strategies. Results Eight randomised trials including 10,532 patients were analysed. In pairwise random-effects analyses, angiography-derived FFR showed no statistically significant differences compared with conventional strategies for MACE (OR 0.77, 95% CI 0.54–1.10), cardiovascular death (OR 0.91, 95% CI 0.56–1.48), MI (OR 0.93, 95% CI 0.55–1.59), or ID-TVR (OR 0.92, 95% CI 0.67–1.26). In the network meta-analysis, angiography-guided PCI was associated with a higher risk of MACE (OR 1.68, 95% CI 1.11–2.53) and MI (OR 1.70, 95% CI 1.24–2.34) compared with angiography-derived FFR guidance. No significant differences were observed between angiography-derived FFR, wire-based FFR, and IVUS-guided strategies across all outcomes. P-score ranking consistently placed wire-based FFR and IVUS highest, angiography-derived FFR intermediate, and angiography-guided PCI lowest. Conclusions Angiography-derived FFR was associated with superior outcomes compared with angiography-guided PCI and demonstrated comparable effectiveness to wire-based FFR and IVUS. These findings position angiography-derived FFR as a clinically meaningful physiological alternative when invasive pressure-wire assessment is not routinely implemented.ESC2026_network_meta_outcomes.