Angiography-derived versus wire-based fractional flow reserve for guiding coronary revascularization: a meta-analysis of randomized controlled trials

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Intermediate coronary artery stenosis (n=6542). Intervention: Angiography-derived FFR-guided revascularization (QFR, vFFR, FFRangio) vs. Invasive pressure-wire-based FFR-guided (or iFR-guided) revascularization. Primary outcome: Major adverse cardiovascular events (MACE) (RR 1.07, 95% CI 0.91-1.27, p=0.41).

Q: What does this research mean for the field?

Angiography-derived fractional flow reserve demonstrates comparable rates of major adverse cardiovascular events to wire-based fractional flow reserve for guiding revascularization, but is associated with higher rates of percutaneous coronary intervention and shorter procedural times. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Peng-Yu Zhong; Qingyi Yang; Lei Liu; Lin He; Wei Ni

doi:10.3389/fcvm.2026.1969354

October 30, 2026Frontiers in Cardiovascular MedicineOpen Access

Angiography-derived versus wire-based fractional flow reserve for guiding coronary revascularization: a meta-analysis of randomized controlled trials

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Key result

Angiography-derived FFR shows no difference in MACE vs. wire-based FFR, despite increasing PCI rates.

RR 1.07
95% CI 0.91-1.27
P=0.41
n=6,542

Why the study?

Invasive pressure-wire-based FFR requires pressure-wire equipment and adenosine-induced hyperemia, and quantitative pooled evidence from patient-level RCTs comparing it with angiography-derived FFR for guiding coronary revascularization remained limited.

Does angiography-derived FFR-guided coronary revascularization reduce major adverse cardiovascular events compared to invasive pressure-wire-based FFR guidance in patients with intermediate coronary artery stenosis?

Key Points

To evaluate the clinical outcomes and procedural efficiency of angiography-derived fractional flow reserve compared with standard invasive wire-based fractional flow reserve for guiding coronary revascularization.
Systematic review and meta-analysis of 4 randomized controlled trials involving 6,542 participants identified across PubMed, Cochrane Library, Embase, and Web of Science Core Collection.
Assessed revascularization guidance using angiography-derived FFR versus wire-based FFR for the primary endpoint of major adverse cardiovascular events (MACE).
Evaluated clinical evidence certainty via GRADE assessment and evaluated sample size adequacy using trial sequential analysis (TSA).
No significant difference was observed for the primary endpoint of MACE between groups (RR 1.07, 95%CI 0.91-1.27), with comparable rates of all-cause mortality, cardiac mortality, recurrent myocardial infarction, unplanned revascularization, and stent thrombosis.
Angiography-derived FFR was associated with significantly higher patient-level PCI rates (RR 1.24, 95%CI 1.15-1.33) and lesion-level PCI rates (RR 1.24, 95%CI 1.18-1.31).
Procedural duration was significantly reduced with angiography-derived FFR (MD −4.09 min, 95%CI −5.76 to −2.43), though TSA revealed insufficient accumulated sample size for most hard clinical endpoints.

Study Design

Type

Meta-Analysis (n=6,542)

Blinding

Open-label

Randomization

Patient-level randomized controlled trials

Multicenter

Yes

Structured PICO

Does angiography-derived FFR-guided coronary revascularization reduce major adverse cardiovascular events compared to invasive pressure-wire-based FFR guidance in patients with intermediate coronary artery stenosis?

P

Population

6,542 older adults (mean age 67.0-71.8 years, ~24.4% female) across 4 RCTs with intermediate coronary artery stenosis scheduled for physiology-guided revascularization, excluding CABG or complex congenital coronary disease, followed for 12 to 24 months.

I

Intervention

Coronary revascularization decision-making guided by wire-free angiography-derived fractional flow reserve (FFR) systems, including QFR version 2.0, vFFR, or FFRangio (revascularization threshold ≤0.80, defer if >0.80).

C

Comparator

Coronary revascularization decision-making guided by invasive pressure-wire-based physiological assessment, primarily adenosine-induced pressure-wire FFR (≤0.80 threshold), with one trial (ALL-RISE) allowing operator-selected FFR (≤0.80) or iFR (≤0.89; 44.5% received iFR).

O

Outcome

Major adverse cardiovascular events (MACE) at 12-month to 2-year follow-up, defined according to each original RCT protocol (composite of all-cause or cardiac death, myocardial infarction, and unplanned/clinically-driven/ischaemia-driven or any revascularization).composite

Main Result

Relative Risk: 1.07 (95% CI 0.91–1.27)

Absolute Event Rate: 7.81% vs 7.26%

p-value: p=0.41

In patients with intermediate coronary stenosis, angiography-derived FFR yields comparable clinical outcomes and shorter procedural times compared to wire-based FFR, though it significantly increases the rate of PCI utilization and remains underpowered for definitive conclusions on hard clinical endpoints.

Limitations

Only four patient-level RCTs were eligible, and trial sequential analysis showed the sample size did not reach the required information size (75,334) for MACE and other hard clinical endpoints.
Heterogeneity existed across trials regarding angiography-derived FFR software versions (QFR, vFFR, FFRangio), computational algorithms, and angiographic image-acquisition protocols.
Interventional operators were unblinded to treatment allocation in all included trials, which could introduce ascertainment bias and influence revascularization decisions.
Follow-up durations varied among studies (12 months vs. 24 months), with limited outcome data beyond 12 months.
The analysis relied on published aggregate trial data rather than individual-patient data, precluding adjusted subgroup analyses.
Control-arm physiological modalities varied slightly, as the ALL-RISE trial permitted operator-selected iFR (44.5% of control arm) in addition to wire-based FFR.
Insufficient sample size for most hard clinical endpoints including MACE on trial sequential analysis (required information size of 75,334 participants not reached)
Operators were unblinded to treatment allocation across all included open-label trials, which may influence revascularization decision-making
Notable methodological and clinical heterogeneities across individual studies (e.g., differing software platforms, MACE definitions, follow-up durations, and inclusion of iFR in one control arm)
Quantitative publication-bias tests were not statistically feasible due to the inclusion of only four eligible RCTs

Implication

No MACE difference supports angiography-derived FFR as a wire-free alternative despite higher PCI rates; extends randomized evidence for functional guidance in CAD.

Abstract

Background Invasive pressure-wire-based fractional flow reserve (FFR) is the reference standard for physiology-guided coronary revascularization, yet it requires pressure-wire equipment and adenosine-induced hyperemia. Angiography-derived FFR enables functional assessment solely from coronary angiograms, while quantitative pooled evidence from patient-level randomized controlled trials (RCTs) remains limited. Methods We searched PubMed, Cochrane Library, Embase and Web of Science Core Collection for eligible RCTs comparing angiography-derived FFR-guided versus wire-based FFR-guided revascularization. The primary endpoint was major adverse cardiovascular events (MACE). Pooled risk ratios or mean differences with 95% confidence intervals were calculated. GRADE assessment and trial sequential analysis (TSA) were performed, and publication bias was evaluated by funnel-plot inspection. Results Four RCTs involving 6,542 participants were included. No significant difference in MACE was observed between groups (RR 1.07, 95%CI 0.91-1.27). All-cause mortality, cardiac mortality, recurrent myocardial infarction, unplanned revascularization and stent thrombosis were also comparable. Angiography-derived FFR was associated with higher patients-level PCI rate (RR 1.24, 95%CI 1.15-1.33), lesion-level PCI rate (RR 1.24, 95%CI 1.18-1.31) and shorter procedural time (MD −4.09 min, 95%CI −5.76 to −2.43). TSA showed insufficient sample size for most hard clinical endpoints. GRADE certainty varied across endpoints, procedural outcomes were rated high-certainty, while most clinical outcomes were of moderate certainty and stent thrombosis of low certainty. Conclusions Relative to wire-based FFR, angiography-derived FFR showed no statistically significant difference in ischaemic-driven clinical outcomes and procedural duration. However, it may increase the likelihood of undergoing PCI. Further large-scale trials with extended follow-up are needed to clarify the long-term implications of this revascularization pattern. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , CRD420261479620.

Discussion

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Cite This Study

Zhong et al. (2026) conducted a meta-analysis in Intermediate coronary artery stenosis (n=6,542). Angiography-derived FFR-guided revascularization (QFR, vFFR, FFRangio) vs. Invasive pressure-wire-based FFR-guided (or iFR-guided) revascularization was evaluated on Major adverse cardiovascular events (MACE) (RR 1.07, 95% CI 0.91-1.27, p=0.41). Angiography-derived FFR showed no significant difference in MACE compared with wire-based FFR (RR 1.07, 95% CI 0.91-1.27, P=0.41) in patients with coronary stenosis, while increasing PCI rates.

synapsesocial.com/papers/6ae682cae432e7a5c4ef375e https://doi.org/10.3389/fcvm.2026.1969354

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Angiography-derived versus wire-based fractional flow reserve for guiding coronary revascularization: a meta-analysis of randomized controlled trials

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Angiography-derived versus wire-based fractional flow reserve for guiding coronary revascularization: a meta-analysis of randomized controlled trials

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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