The prognostic value of regadenoson stress: Has the case been made?
Received May
The prognostic value of regadenoson stress: Has the case been made?
Rami Doukky 1
MSc 1
FACC 1
FASNC 1 2 3
0 3620 , Chicago, IL , 60612; rami_doukky @rush.edu J Nucl Cardiol 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology
1 Reprint requests: Rami Doukky , MD, MSc, FACC , FASNC Division of Cardiology, John H. Stroger, Jr. Hospital of Cook County , 1901 W. Harrison St., Suite
2 Division of Cardiology, Rush University Medical Center , Chicago, IL
3 Division of Cardiology, John H. Stroger, Jr. Hospital of Cook County , Chicago, IL
Since its approval by the Food and Drug Administration in April of 2008, regadenoson has enjoyed a wide implementation by nuclear cardiology laboratories. Presently, it is the preferred vasodilator stress agent in the United States, being used in 8 out of 10 pharmacologic stress SPECT myocardial perfusion imaging (MPI) studies.1 The initial approval of regadenoson was based on two phase 3 ADVANCE-MPI trials, in which regadenoson was demonstrated to produce perfusion defects similar to those induced by standard 6 minute adenosine infusion.2,3 Although diagnostic noninferiority of regadenoson was effectively demonstrated, prognostic noninferiority was beyond the scope of the ADVANCE-MPI trials. Nonetheless, given the similarity in perfusion images, the prognostic value of regadenoson stress was presumed to parallel that of adenosine. In nuclear cardiology, a field that prides itself on vast wealth of outcomes data, extending the prognostic utility of adenosine to regadenoson is just not good enough. In recent years, several studies have investigated the prognostic value of regadenoson stress MPI. Iqbal et al compared the 2-year outcome of patients with normal regadenoson MPI (n = 1,000) to those with normal adenosine MPI (n = 1,000) for the composite endpoint of cardiac death, myocardial infarction, and coronary revascularization.4 The annual event rate was
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1.1% in the regadenoson group and 1.7% in the
adenosine group (P = 0.090) and the annual cardiac death rate
was 0.9% and 1.15% (P = 0.404), respectively. In
propensity score matched analysis of 505 patients from
each group, the respective annual event rates in the
regadenoson and adenosine groups were 0.7% and 1.3%
(P = 0.257) for the primary outcome, and 0.5% and
0.7% (P = 0.763) for cardiac death. Thus, the study
effectively demonstrated that, as with normal adenosine
MPI, a normal regadenoson MPI predicts very low event
rates.4 More recently, Hage et al evaluated the
prognostic value of regadenoson stress in 1,400 subjects (700
consecutive normal MPI and 700 consecutive abnormal
MPI).5 Based on the quantitative perfusion defect size
(percentage of left ventricular myocardium), the cohort
was divided into four groups: Group 1, normal (\5%);
Groups 2, small defect (\10%); Group 3, moderate sized
defect (10%-20%); Group 4, large defect ([20%).
During a mean follow-up of 4 years, the composite
endpoint of cardiac death, myocardial infarction, and
late coronary revascularization ([90 days after MPI)
occurred in 10, 27, 31, and 43% (P \ 0.001); while
early revascularization (\90 days) occurred in 0.4, 9,
17, and 17% in Groups 1-4, respectively (P \ 0.001).
The authors demonstrated a step-wise increase in event
rates commensurate with the size of
regadenoson-induced defect. The study showed that, as with other stress
agents, regadenoson MPI provides powerful prognostic
information which can guide clinical decision-making.5
In this issue of the journal, Farzaneh-Far et al
compared the prognostic value of regadenoson and
adenosine MPI in 3,698 consecutive patients (1,737
adenosine and 1,961 regadenoson) followed for 1 year.6
The cohort included patients with normal and abnormal
MPI, unlike the study by Iqbal et al which analyzed
patients with normal MPI. The investigators used
inverse probability weighted Cox proportional hazards
regression modeling to balance the baseline
characteristics associated with each vasodilator agent.
Irrespective of the vasodilator choice, the Summed
Stress Score (SSS) remained a significant predictor of
the composite endpoint of cardiovascular death or
myocardial infarction (hazard ration [HR], 1.36 per 5%
increment; 95% confidence interval [CI] 1.28-1.46;
P \ 0.0001) and cardiovascular death (HR, 1.38 per 5%
increment; CI 1.28-1.49; P \ 0.0001). Similarly, the
Summed Difference Score (SDS) was a significant
predictor of the composite of cardiovascular death and
myocardial infarction (HR, 1.61 per 5% increment; CI
1.38-1.88; P \ 0.001) and cardiovascular death (HR
1.46 per 5% increment; CI 1.22-1.75; P \ 0.001).
Importantly, there was no significant interaction between
SSS and stress agent or between SDS and stress agent as
determinants of any of the study endpoints. In other
words, SSS and SDS derived from adenosine or
regadenoson MPI rendered similarly significant prognostic
value. This is an important finding; it affirms
comparable prognostic significance of perfusi (...truncated)