The new england journal of medicine n engl j med nejm.org 1 original article Fractional Flow Reserve–Guided PCI versus Medical Therapy in Stable Coronary Disease Bernard De Bruyne, M.D., Ph.D., Nico H.J. Pijls, M.D., Ph.D., Bindu Kalesan, M.P.H., Emanuele Barbato, M.D., Ph.D., Pim A.L. Tonino, M.D., Ph.D., Zsolt Piroth, M.D., Nikola Jagic, M.D., Sven Mobius-Winckler, M.D., Gilles Rioufol, M.D., Ph.D., Nils Witt, M.D., Ph.D., Petr Kala, M.D., Philip MacCarthy, M.D., Thomas Engström, M.D., Keith G. Oldroyd, M.D., Kreton Mavromatis, M.D., Ganesh Manoharan, M.D., Peter Verlee, M.D., Ole Frobert, M.D., Nick Curzen, B.M., Ph.D., Jane B. Johnson, R.N., B.S.N., Peter Jüni, M.D., and William F. Fearon, M.D., for the FAME 2 Trial Investigators* From the Cardiovascular Center Aalst, Onze-Lieve-Vrouw Clinic, Aalst, Belgium (B.D.B., E.B.); Department of Cardiology, Catharina Hospital, and Department of Biomedical Engineering, Eindhoven Univer- sity of Technology — both in Eindhoven, the Netherlands (N.H.J.P., P.A.L.T.); Divi- sion of Clinical Epidemiology and Biosta- tistics, Institute of Social and Preventive Medicine and Clinical Trials Unit Bern, University of Bern, Bern, Switzerland (B.K., P.J.); Hungarian Institute of Cardiology, Budapest (Z.P.); Clinical Center Kragujevac, Kragujevac, Serbia (N.J.); Heart Center Leipzig, Leipzig, Germany (S.M.-W.); Car- diovascular Hospital, Lyon, France (G.R.); Sodersjukhuset, Stockholm (N.W.), and Örebro University Hospital, Örebro (O.F.) — both in Sweden; Department of Inter- nal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic (P.K.); King’s College Hospital, London (P.M.), Golden Jubilee National Hospital, Glasgow (K.G.O.), Royal Victoria Hospi- tal, Belfast (G.M.), and Department of Cardiology, Southampton University Hos- pital Trust, Southampton (N.C.) — all in the United Kingdom; Department of Car- diology, Rigshospitalet University Hospi- tal, Copenhagen (T.E.); Atlanta Veterans Affairs Medical Center, Atlanta (K.M.); Northeast Cardiology Associates, Bangor, ME (P.V.); St. Jude Medical, Plymouth, MN (J.B.J.); and Stanford University Medical Center, Stanford, CA (W.F.F.). Address reprint requests to Dr. De Bruyne at the Cardiovascular Centre Aalst, OLV-Clinic, Moorselbaan 164, B-9300 Aalst, Belgium, or at bernard.de.bruyne@olvz-aalst.be. *The investigators in the Fractional Flow Reserve versus Angiography for Multi- vessel Evaluation 2 (FAME 2) trial are listed in the Supplementary Appendix, available at NEJM.org. This article was published on August 28, 2012, at NEJM.org. N Engl J Med 2012. DOI: 10.1056/NEJMoa1205361 Copyright © 2012 Massachusetts Medical Society. Abstract Background The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone. Methods In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end- point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The dif- ference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were trig- gered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event. Conclusions In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.) The New England Journal of Medicine Downloaded from nejm.org on August 27, 2012. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. All rights reserved.