Long‐Term Outcomes of iFR‐ Versus FFR‐Guided Coronary Physiology in Real‐World Clinical Practice

BACKGROUND: Fractional flow reserve (FFR) is the reference standard for invasive physiological assessment of intermediate coronary stenoses. Instantaneous wave-free ratio (iFR) was introduced as a non-hyperemic alternative, and the DEFINE-FLAIR and iFR-SWEDEHEART trials demonstrated noninferiority of iFR- versus FFR-guided management at 1 year, leading to widespread adoption of iFR. However, long-term follow-up and pooled analyses subsequently suggested higher all-cause mortality with iFR-guided assessment. We therefore compared long-term outcomes of iFR- versus FFR-guided coronary physiology assessment in real-world clinical practice. METHODS: This retrospective single-center study included consecutive patients undergoing invasive physiological assessment between 2012 and 2022. Patients were managed according to FFR- or iFR-guided strategies, with revascularization performed for physiologically significant lesions and deferred otherwise. The primary endpoint was all-cause mortality. Secondary endpoints included major adverse cardiovascular events (death from any cause, myocardial infarction or unplanned revascularization), and the individual componentes of the secondary composite endpoint. Time-to-event analyses were performed using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: A total of 1104 patients were included, comprising 428 patients in the FFR group and 676 in the iFR group. Baseline clinical characteristics were well balanced between groups. Functionally significant stenoses were less frequently identified in the iFR group (42% vs. 49%, p = 0.001), resulting in higher rates of revascularization deferral. During long-term follow-up, iFR-guided management was associated with significantly higher all-cause mortality compared with FFR-guided management (HR 1.52, 95% CI 1.19-1.93; p < 0.001). The incidence of MACE was also significantly higher with iFR (HR 1.47, 95% CI 1.19-1.82; p < 0.001), driven by mortality, with no differences in myocardial infarction or unplanned revascularization. CONCLUSIONS: In this large real-world cohort, iFR-guided coronary physiological assessment was associated with higher long-term all-cause mortality and MACE compared with FFR-guided management, while rates of myocardial infarction and unplanned revascularization were similar. These findings parallel long-term observations from randomized clinical trials and support the need for further studies evaluating the prognostic implications of resting versus hyperemic physiological indices.