Quantitative flow ratio (QFR) uses coronary angiograms to estimate whether a narrowing limits blood flow. A prespecified secondary analysis of the FAVOR III China randomized trial reports fewer major adverse cardiac events at three years with QFR-guided PCI in patients with multivessel disease. The key qualification is that the analysis did not demonstrate a statistically significant difference in treatment effect between patients with and without multivessel disease.
Why Quantitative Flow Ratio Matters
Visual angiography describes the shape and apparent severity of coronary narrowing, but anatomical appearance does not always establish its physiologic importance. QFR applies computational analysis to angiographic images to estimate a pressure-based measure of lesion significance without adding a coronary pressure wire or administering a hyperemic drug. In this study, it was used to refine an intervention plan originally based on visual angiography.
Zhang and colleagues examined whether multivessel disease influenced the longer-term findings of FAVOR III China. Their report addresses the selection of lesions for PCI. It does not compare PCI with coronary artery bypass grafting, evaluate an extracorporeal support strategy, or establish that QFR is equivalent to invasive fractional flow reserve.
Study Design and Population
The original trial enrolled patients across 26 Chinese centers between December 2018 and January 2020. The present analysis included 3,825 participants after 22 randomized patients withdrew permission to use their data. Mean age was 62.7 years, and 70.6% were men. Multivessel disease was present in 2,066 patients, or 54.0% of the analyzed population.
Eligible participants were adults being considered for PCI who had at least one visually estimated 50% to 90% stenosis in a vessel at least 2.5 mm in diameter. Clinical presentations included stable or unstable angina and myocardial infarction occurring at least 72 hours before screening. Multivessel disease meant at least 50% narrowing in two or more epicardial vessels or in the left main coronary artery.
Participants were randomized to QFR-guided or angiography-guided treatment. In the QFR arm, lesions with values at or below 0.80 were treated, whereas those above 0.80 were deferred; lesions exceeding 90% angiographic stenosis were also treated. Patients whose assessed lesions did not meet the intervention criteria could receive medical treatment alone. Staged PCI within 60 days was permitted for multivessel disease.
Three-Year Clinical Outcomes
The outcome examined here was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, and ischemia-driven revascularization. Although the parent trial’s primary endpoint was assessed at one year, this publication evaluates outcomes at three years according to multivessel disease status.
| Three-year MACE | QFR guidance | Angiography guidance | Hazard ratio (95% CI) |
|---|---|---|---|
| Multivessel disease | 124 events; 12.1% | 188 events; 18.1% | 0.65 (0.52–0.81) |
| Without multivessel disease | 76 events; 8.6% | 95 events; 11.0% | 0.77 (0.57–1.04) |
In the multivessel cohort, the reported event rates differed by 6.0 percentage points. The lower composite event rate was driven by fewer myocardial infarctions and ischemia-driven repeat procedures. Myocardial infarction occurred at reported rates of 5.5% versus 9.5%, while ischemia-driven revascularization occurred at 6.5% versus 9.2%. The analysis did not demonstrate a statistically significant all-cause mortality reduction.
Why the Interaction Test Is Essential
A statistically significant result in one subgroup and a nonsignificant result in another do not, by themselves, establish that the treatment works differently in those populations. The direct interaction test addresses that question. Here, P = .35 provides no statistically significant evidence that multivessel disease modified the treatment effect.
The smaller number of events among patients without multivessel disease produced a less precise estimate, with a confidence interval crossing 1.0. That finding neither proves absence of benefit nor establishes equivalence between strategies. The defensible interpretation is a clearer within-subgroup benefit in the multivessel cohort, accompanied by uncertainty about whether the true treatment effects differ across disease strata.
How Physiology Changed the PCI Plan
QFR frequently changed which vessels operators treated. Among patients with multivessel disease, strategy modification occurred in 29.4% of the QFR group versus 10.1% of the angiography group. Deferral of at least one originally intended vessel occurred in 22.6% versus 8.4%; treatment of a vessel not originally planned for intervention occurred in 8.1% versus 2.4%.
Functionally complete revascularization was reported in 82.5% versus 72.6% of assessed multivessel patients. This term meant the absence of a remaining vessel with a QFR at or below 0.80. It describes physiologic completeness, which differs from eliminating every visible anatomical narrowing. Fewer average stents and more selective intervention can therefore coexist with better functional completeness.
Limits and Comparison With Pressure-Wire Assessment
This was a prespecified secondary analysis, but subgroup comparisons were underpowered. Additional endpoint, landmark, and hierarchical analyses are exploratory. Operators knew the assigned treatment during PCI, and patients and follow-up personnel became unblinded after one year. Knowledge of treatment could influence subsequent management, especially decisions about repeat revascularization.
The multivessel cohort had relatively modest anatomical complexity, with a mean SYNTAX score near 12 and a small proportion of left main disease. Results may not generalize to highly complex coronary anatomy. QFR also depends on adequate angiographic acquisition, so its performance cannot be separated from image quality and technique.
The authors explicitly distinguish this comparison from FAVOR III Europe, which did not establish QFR noninferiority to invasive FFR guidance. Better outcomes than angiography alone do not establish interchangeability with pressure-wire physiology. Similarly, these data do not determine whether an individual patient should receive PCI or surgery.
Relevance for Perfusion and Heart Teams
For perfusionists and multidisciplinary cardiovascular teams, the educational value lies in understanding how functional lesion assessment can change revascularization plans. The study supports discussion of myocardial ischemia, residual disease burden, and the distinction between anatomical and functional completeness. It supplies no validated bypass-management protocol, mechanical-support indication, or patient-specific treatment rule.
Study Ranking and Rationale
IPA evidence ranking: 4/5 — high quality. The analysis draws on a large multicenter randomized trial, a prespecified disease subgroup, independent blinded event adjudication, and three-year follow-up. A secondary subgroup analysis, limited interaction-test power, operator unblinding, later follow-up unblinding, and restricted anatomical complexity prevent the strongest rating and limit subgroup-specific claims.
The publication reports public and institutional research funding, with no stated funder role in study conduct or reporting. Pulse Medical supplied the original trial’s QFR system and software without charge; an author disclosed being a company cofounder and receiving related research grants. Additional cardiovascular industry relationships are disclosed in the original article.
Original Article
Zhang H, Shi Y, Guan C, et al; FAVOR III China Study Group. Quantitative Flow Ratio– vs Angiography-Guided Percutaneous Coronary Intervention: A Secondary Analysis of the FAVOR III China Trial. JAMA Network Open. 2026;9(10):e2639926. Published October 22, 2026. doi:10.1001/jamanetworkopen.2026.39926.
This independently written IPA educational synthesis accompanies the unchanged source publication, distributed under CC BY-NC-ND terms. The cover is an AI-generated editorial illustration.
