In patients with stable coronary artery disease (CAD), the long-term benefits of revascularization over medical therapy remain unclear. In the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 trial, patients with hemodynamically significant stenoses (fractional flow reserve (FFR) ≤ 0.80) were randomized to receive FFR-guided percutaneous coronary intervention (PCI) plus medical therapy (n = 447) or medical therapy alone (n = 441). At 5 years, FFR-guided PCI reduced the risk of the primary composite outcome of time to death, myocardial infarction or urgent revascularization, largely because of fewer urgent revascularizations. We now report the long-term clinical outcomes from this trial. Sixteen hospitals, contributing 748 randomized patients (161 women, 21.5%), participated in the long-term follow-up. The primary composite outcome was analyzed hierarchically using the unstratified win ratio, which addressed differential missingness of data on nonfatal outcomes in deceased patients by prioritizing comparisons on time to death. At a median follow-up of 11.2 years, the primary endpoint occurred in 150 of 447 patients (33.6%) in the PCI group versus 182 of 441 (41.3%) in the medical therapy group. PCI was superior in 29.2% of comparisons, medical therapy in 23.3%, and the two groups were tied in 47.5%, resulting in a win ratio of 1.25 in favor of PCI (95% confidence interval (CI) 1.01-1.56, P = 0.043). The corresponding win difference was 5.9% (95% CI 0.2-11.6), and the number needed to treat was 17 (95% CI 9-500). Win ratios were 0.88 for all-cause death (95% CI 0.66-1.17), 1.50 for myocardial infarction (95% CI 0.98-2.31) and 4.57 for urgent revascularization (95% CI 2.53-8.24). During long-term follow-up, FFR-guided PCI in patients with stable CAD and hemodynamically significant stenoses reduced the composite of death, myocardial infarction or urgent revascularization, primarily because of fewer urgent revascularizations. These long-term findings reaffirm the efficacy of FFR-guided PCI over medical therapy in patients with stable CAD. ClinicalTrials.gov registration: NCT06159231 .

Atlanta VA Medical Center Emory University Atlanta GA USA

Cardiology Unit Azienda Ospedaliera Universitaria di Ferrara Ferrara Italy

Cardiovascular Center Aalst AZORG Aalst Belgium

Clinical Hospital Center Zemun Beograd Serbia

Clinical Trial Service Unit and Epidemiological Studies Unit Nuffield Department of Population Health University of Oxford Oxford UK

Department of Biomedical Engineering Eindhoven University of Technology Eindhoven the Netherlands

Department of Cardiology Catharina Hospital Eindhoven the Netherlands

Department of Cardiology Lausanne University Hospital Lausanne Switzerland

Department of Cardiology Örebro University Hospital Örebro Sweden

Department of Cardiology Tokyo Medical University Hachioji Medical Center Tokyo Japan

Department of Clinical and Molecular Medicine Sapienza University of Rome Rome Italy

Department of Clinical Medicine Aarhus University Aarhus Denmark

Department of Clinical Pharmacology Aarhus University Hospital Aarhus Denmark

Department of Clinical Science and Education Unit of Cardiology Karolinska Institute Södersjukhuset Stockholm Sweden

Department of Internal Medicine University of Kragujevac Kragujevac Serbia

Department of Medicine 1 University Hospital Munich Ludwig Maximilian University of Munich Munich Germany

Division of Cardiovascular Medicine and Stanford Cardiovascular Institute Stanford University School of Medicine and VA Palo Alto Health Care System Palo Alto CA USA

Division of Clinical Pharmacology Department of Pharmacology Showa University Tokyo Japan

Gottsegen National Cardiovascular Center Budapest Hungary

Heart Center Leipzig at University of Leipzig Leipzig Germany

Hospices Civils de Lyon and Claude Bernard University Lyon France

Medical Faculty of Masaryk University and University Hospital Brno Brno Czech Republic

Na Homolce Hospital Prague Czech Republic

Northeast Cardiology Associates Bangor ME USA

Rigshospitalet University of Copenhagen Copenhagen Denmark

Steno Diabetes Center Aarhus Aarhus University Hospital Aarhus Denmark

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ClinicalTrials.gov
NCT06159231