Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Coronary Artery Disease
Abstract
BACKGROUND: ORBITA-2 (the Placebo-Controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina) provided evidence for the role of percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are often used to guide PCI; however, their ability to predict placebo-controlled angina improvement is unknown. METHODS: Participants with angina, ischemia, and stable coronary artery disease were enrolled, and anti-anginal medications were stopped. Participants reported angina episodes daily for 2 weeks using the ORBITA smartphone symptom application (ORBITA-app). At the research angiogram, FFR and iFR were measured. After sedation and auditory isolation, participants were randomized to PCI or placebo before entering a 12-week blinded follow-up phase with daily angina reporting. The ability of FFR and iFR, analyzed as continuous variables, to predict the placebo-controlled effect of PCI was tested using Bayesian proportional odds modeling. RESULTS: Invasive physiology data were available for 279 patients (140 PCI and 139 placebo). The median (interquartile range) age was 65 years (59.0–70.5), and 223 (79.9%) were male. Median FFR was 0.60 (0.46–0.73), and median iFR was 0.76 (0.50–0.86). The lower the FFR or iFR, the greater the placebo-controlled improvement with PCI across all end points. There was strong evidence that a patient with an FFR at the lower quartile would have a greater placebo-controlled improvement in angina symptom score with PCI than a patient at the upper quartile (FFR, 0.46 versus 0.73: odds ratio, 2.01; 95% credible interval, 1.79–2.26; probability of interaction, >99.9%). Similarly, there was strong evidence that a patient with an iFR at the lower quartile would have greater placebo-controlled improvement in angina symptom score with PCI than a patient with an iFR at the upper quartile (iFR, 0.50 versus 0.86: odds ratio, 2.13; 95% credible interval, 1.87–2.45; probability of interaction, >99.9%). The relationship between benefit and physiology was seen in both Rose angina and Rose nonangina. CONCLUSIONS: Physiological stenosis severity, as measured by FFR and iFR, predicts placebo-controlled angina relief from PCI. Invasive coronary physiology can be used to target PCI to those patients who are most likely to experience benefit. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03742050.
Article Details
Authors (76)
Michael J. Foley
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Christopher A. Rajkumar
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Shayna Chotai
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
John R. Davies
Mid and South Essex NHS Foundation Trust, Basildon, United Kingdom
Thomas R. Keeble
Essex Cardiothoracic Centre, Mid and South Essex NHS Foundation Trust, Basildon, UK (K.K., S.R.M., T.R.K., J.R.D., G.C., J.N.D.).
Sukhjinder S. Nijjer
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Graham D. Cole
National Heart and Lung Institute, Imperial College London, London, UK (C.A.R., M.J.F., F.A.-J., S.C., F.A.S., M.M., A.S., S.G., R.P., G.D.C., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
James P. Howard
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Darrel P. Francis
Matthew J. Shun-Shin
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Christopher Rajkumar
Imperial College London, London, United Kingdom
Michael Foley
Imperial College London, London, United Kingdom
Fiyyaz Ahmed-Jushuf
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Florentina Simader
Imperial College London, London, United Kingdom
Sashiananthan Ganesananthan
National Heart and Lung Institute, Imperial College London, London, UK (C.A.R., M.J.F., F.A.-J., S.C., F.A.S., M.M., A.S., S.G., R.P., G.D.C., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Danqi Wang
Muhammad Mohsin
Rachel Pathimagaraj
Brian Wang
Albert Einstein College of Medicine, Brooklyn, New York, United States
Krzysztof Macierzanka
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Ricardo Petraco
National Heart and Lung Institute, Imperial College London, London, UK (C.A.R., M.J.F., F.A.-J., S.C., F.A.S., M.M., A.S., S.G., R.P., G.D.C., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Ramzi Khamis
Imperial College London, London, United Kingdom
Graham Cole
Imperial College Healthcare NHS, London, United Kingdom
James Howard
Imperial College London, London, United Kingdom
Jamil Mayet
Darrel Francis
Imperial College London, London, United Kingdom
Matthew Shun-Shin
Imperial College London, London, United Kingdom
Rasha Al-Lamee
National Heart and Lung Institute, Imperial College London, London
Arif Kokhar
Aisha Gohar
Ioannis Lampadakis
Henry Seligman
National Heart and Lung Institute, Imperial College London, UK (F.A.-J., M.J.F., S.C., C.A.R., D.W., F.A.S., K.M., K.C., S.M., S.S.N., H.S., J.P.H., D.P.F., M.J.S.-S., R.K.A.-L.).
Sukhjinder Njjer
Sayan Sen
One Heart Clinic, London, UK (S.S.).
Punit Ramrakha
Raffi Kaprielian
Iqbal Malik
Masood Khan
Amarjit Sethi
Rodney Foale
Thomas Keeble
Essex Cardiothoracic Centre, Basildon, United Kingdom
Kare Tang
Essex Cardiothoracic Centre, Mid and South Essex NHS Foundation Trust, Basildon, UK (J.N.D., A.K., K.T., R.G., J.R.D., T.R.K., G.J.C.).
John Davies
Essex Cardiothoracic Centre, Basildon, United Kingdom
Reto Gamma
Essex Cardiothoracic Centre, Mid and South Essex NHS Foundation Trust, Basildon, UK (J.N.D., A.K., K.T., R.G., J.R.D., T.R.K., G.J.C.).
Gerald Clesham
Essex Cardiothoracic Centre, Mid and South Essex NHS Foundation Trust, Basildon, UK (K.K., S.R.M., T.R.K., J.R.D., G.C., J.N.D.).
Jason Dungu
Alamgir Kabir
Shah Mohd Nazri
Peter O’Kane
Department of Cardiology, Royal Bournemouth Hospital, Bournemouth, United Kingdom
Jonathan Hinton
University Hospitals Dorset NHS Foundation Trust, Bournemouth, UK (J.N.D., P.D.O., J.H.).
Jehangir Din
Department of Cardiology, University Hospitals of Dorset NHS Foundation Trust, Bournemouth, United Kingdom (P.O., J.D.).
Alexandra Nowbar
Tushar Kotecha
Royal Free London NHS Foundation Trust, UK (D.K., T.K.).
Peter Haworth
Portsmouth Hospitals University NHS Trust, UK (P.H.).
James Spratt
St George's Hospital, London, United Kingdom
Rupert Williams
St George’s, University of London and St. George’s University Hospitals NHS Foundation Trust, UK (R.W., J.C.S.).
Claudia Cosgrove
St George's Hospital, London, United Kingdom
Pitt Lim
Helen Routledge
Department of Cardiology, Worcestershire Acute Hospitals NHS Trust, Worcester, United Kingdom (H.R.).
Lal Mughal
Jasper Trevelyan
Worcestershire Acute Hospital NHS Trust, UK (J.T.).
Manas Sinha
Department of Cardiology, Salisbury Hospital NHS Foundation Trust, United Kingdom (M.S.).
Nick Curzen
University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
James Wilkinson
Vanderbilt University School of Medicine, Nashville, Tennessee, United States
Rohit Sirohi
Alison Calver
John Rawlins
University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Richard Jabbour
Neil Ruparelia
Joban Sehmi
West Hertfordshire Hospitals NHS Trust, Watford, UK (J.S.).
Tim Kinnaird
Faculty of Science, School of Earth and Environmental Sciences, University of St. Andrews
Fairoz Abdul
Vasileios Panoulas
Harefield Hospital, Harefield, United Kingdom
Afzal Sohaib
David Collier
Frank E. Harrell
Vanderbilt University School of Medicine, Nashville, TN (F.E.H.).