Fractional flow reserve and instantaneous wave-free ratio as predictors of the placebo-controlled response to percutaneous coronary intervention in stable coronary artery disease

<p dir="ltr">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. </p><p dir="ltr">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. </p><p dir="ltr">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. </p><p dir="ltr">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. </p><p dir="ltr">Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03742050.</p>