Fractional Flow Reserve and Instantaneous Wave-Free Ratio as Predictors of the Placebo-Controlled Response to Percutaneous Coronary Intervention in Stable Coronary Artery Disease
Authors: Foley Michael J. , Rajkumar Christopher A. , Ahmed-Jushuf Fiyyaz , Simader Florentina , Chotai Shayna , Seligman Henry , Macierzanka Krzysztof , Davies John R. , Keeble Thomas R. , O’Kane Peter , Haworth Peter , Routledge Helen , Kotecha Tushar , Clesham Gerald , Williams Rupert , Din Jehangir , Nijjer Sukhjinder S. , Curzen Nick , Sinha Manas , Petraco Ricardo , Spratt James , Sen Sayan , Cole Graham D. , Harrell Frank E. , Howard James P. , Francis Darrel P. , Shun-Shin Matthew J. , Al-Lamee Rasha , Rajkumar Christopher , Foley Michael , Ahmed-Jushuf Fiyyaz , Simader Florentina , Ganesananthan Sashiananthan , Wang Danqi , Mohsin Muhammad , Pathimagaraj Rachel , Wang Brian , Macierzanka Krzysztof , Petraco Ricardo , Khamis Ramzi , Cole Graham , Howard James , Mayet Jamil , Francis Darrel , Shun-Shin Matthew , Al-Lamee Rasha , Kokhar Arif , Gohar Aisha , Lampadakis Ioannis , Seligman Henry , Njjer Sukhjinder , Sen Sayan , Ramrakha Punit , Kaprielian Raffi , Malik Iqbal , Khan Masood , Sethi Amarjit , Foale Rodney , Keeble Thomas , Tang Kare , Davies John , Gamma Reto , Clesham Gerald , Dungu Jason , Kabir Alamgir , Nazri Shah Mohd , O’Kane Peter , Hinton Jonathan , Din Jehangir , Nowbar Alexandra , Kotecha Tushar , Haworth Peter , Spratt James , Williams Rupert , Cosgrove Claudia , Lim Pitt , Routledge Helen , Mughal Lal , Trevelyan Jasper , Sinha Manas , Curzen Nick , Wilkinson James , Sirohi Rohit , Calver Alison , Rawlins John , Jabbour Richard , Ruparelia Neil , Sehmi Joban , Kinnaird Tim , Abdul Fairoz , Panoulas Vasileios , Sohaib Afzal , Collier David , Harrell Frank E. 
Published: October 2024

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.