Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: a prospective, randomized, multicenter study

Abstract

A multicenter, double-blind, randomized study was conducted to assess the effect of caffeine on regadenoson stress myocardial perfusion imaging (MPI). Subjects with a high likelihood of coronary artery disease underwent a rest single-photon emission computed tomography MPI on day 1 (MPI-1) and a stress MPI with regadenoson on day 3 (MPI-2). Individuals with ≥1 segment with a reversible defect received double-blind caffeine tablets (200 or 400 mg) or placebo 90 min before a repeat regadenoson stress MPI (MPI-3) on day 5. Overall, 207 subjects completed the study (caffeine 200 mg, n = 70; caffeine 400 mg, n = 71; placebo, n = 66). The mean number of segments with reversible defects decreased from MPI-2 to MPI-3 in the caffeine 200 and 400 mg groups versus no significant change in the placebo group [mean ± standard deviation: -0.61 ± 1.097, -0.62 ± 1.367, and 0.12 ± 0.981, respectively (overall treatment effect, P < 0.001)]. The majority of subjects who received caffeine shifted to a lower ischemia size category from MPI-2 to MPI-3, with no clear pattern observed in subjects who received placebo. For caffeine exposed patients with ≥3 segments with reversible defects at MPI-2, 21/23 had fewer detected at MPI-3. Both the 200 and 400 mg doses of caffeine significantly reduced the number of segments with reversible defects detected by regadenoson stress MPI.

Fig. 1

Patient disposition. *Data was not collected on the number of subjects screened, only those randomized. ^†Received randomized treatment at MPI-3 (regadenoson plus placebo or caffeine). ^‡All subjects with interpretable MPI-1, MPI-2, and MPI-3 scans

Fig. 2

Example images. Patient 1 images show a predominantly reversible inferior left ventricular defect (yellow arrows), and a predominantly reversible defect at the left ventricular apex (white arrows). Both defects are more intense after regadenoson stress (b) than after regadenoson plus caffeine 200 mg (c). There is also a nonreversible defect infero-laterally. Patient 2 images show a partially reversible inferior left ventricular defect (white arrows). The defect is larger and more intense after regadenoson stress (b) than after regadenoson plus caffeine 200 mg (c)

Fig. 3

Number of segments with reversible defects detected during MPI 2 and MPI 3 in patients who received placebo (a) and caffeine (b)

Fig. 4

Median number of segments with reversible defects detected at MPI-2 and MPI-3 in subjects with ≥3 segments with reversible defects at MPI-2 who received placebo (a) or caffeine 200 or 400 mg (b) at MPI-3

Fig. 5

Summed difference scores (SDS) at MPI-2 and MPI-3 in subjects with a SDS score ≥2 who received placebo (a) or caffeine 200 or 400 mg (b) at MPI-3

Fig. 6

Mean (±SD) systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate at MPI-3*. *Blood pressure and heart rate data not available for all subjects at all timepoints