The second phase-3 multi-center trial of flurpiridaz F-18 PET myocardial perfusion imaging for coronary artery disease evaluation

Abstract

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in obese patients (0.79 vs 0.67, p<0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.