Fractional flow reserve versus intravascular ultrasound guidance for percutaneous coronary intervention in intermediate coronary stenoses: A systematic review and meta‐analysis

Abstract Intermediate coronary stenoses (40–70% diameter narrowing) pose a diagnostic challenge, as angiography alone often leads to inappropriate revascularization. Whether fractional flow reserve (FFR) or intravascular ultrasound (IVUS) guidance yields superior outcomes remains unclear. This Preferred Reporting Items for Systematic Reviews and Meta‐Analyses‐compliant systematic review and meta‐analysis searched PubMed, Embase, ScienceDirect, and ClinicalTrials.gov from inception to November 2025. Eligible studies were RCTs or observational comparisons of FFR‐ or angiography‐derived FFR versus IVUS‐guided percutaneous coronary intervention (PCI) in intermediate or angiographically significant lesions with ≥12‐month follow‐up. Pooled risk ratios (RR) and mean differences were calculated using random‐effects models. Evidence certainty was graded using GRADE. Six studies (2 RCTs, 4 observational; n = 5050) were included. No significant difference was found in major adverse cardiac events (MACE: RR 1.17, 95% confidence interval CI 0.99–1.39; p = .06) or all‐cause mortality (RR 1.05, 95% CI 0.79–1.38; p = .74). Myocardial infarction rates were similar (RR 1.48, 95% CI 0.88–2.51; p = .14). Ischemia‐driven target vessel revascularization was significantly higher with FFR guidance (RR 1.43, 95% CI 1.07–1.91; p = .02). Mean stent length was numerically shorter with FFR (mean difference −2.07 mm, 95% CI −4.87 to 0.73; p = .15). Evidence certainty was moderate for MACE and target vessel revascularization, low for hard endpoints, and very low for stent length. In intermediate and angiographically significant coronary stenoses, FFR‐ and IVUS‐guided PCI showed comparable hard clinical outcomes, but IVUS was associated with reduced target vessel revascularization. These findings support individualized modality selection based on clinical context and operator expertise, with a potential role for hybrid approaches combining physiological assessment for deferral decisions and imaging for procedural optimization.