A1 Refereed original research article in a scientific journal
Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease
Authors: Jamshid Maddahi, Joel Lazewatsky, James E. Udelson, Daniel S. Berman, Rob S.B. Beanlands, Gary V. Heller, Timothy M. Bateman, Juhani Knuuti, Cesare Orlandi
Publisher: Elsevier USA
Publication year: 2020
Journal:Journal of the American College of Cardiology
Journal name in sourceJournal of the American College of Cardiology
Volume: 76
Issue: 4
First page : 391
Last page: 401
Number of pages: 11
ISSN: 0735-1097
eISSN: 1558-3597
DOI: https://doi.org/10.1016/j.jacc.2020.05.063
Web address : https://www.sciencedirect.com/science/article/pii/S0735109720355315?via%3Dihub
Background
Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer.
Objectives
This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m–labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated.
Methods
In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m–labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data.
Results
Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated.
Conclusions
Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710)
