Comparison of the Short-Term Survival Benefit
Associated with Revascularization Compared with
Medical Therapy in Patients with No Prior
Coronary Artery Disease Undergoing Stress
Myocardial Perfusion Single Photon Emission
Computed Tomography
Rory Hachamovitch, MD, MSc; Sean W. Hayes,
MD; John D. Friedman, MD; Ishac Cohen PhD;
Daniel S. Berman, MD
Published in Circulation 2003
Revascularization vs Medical Therapy After Stress
SPECT: Background
• The relationship between the amount of inducible
ischemia present on stress myocardial perfusion
Single Photon Emission Computed Tomography
(SPECT) (myocardial perfusion stress [MPS]) and the
presence of a short-term survival benefit with early
revascularization versus medical therapy is not clearly
defined.
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs Medical Therapy After Stress
SPECT: Study Design
10,627 consecutive patients who underwent exercise or adenosine MPS and
had no prior MI or revascularization
Mean follow-up 1.9+/- 0.6 years for 90.6% of patients completed.
Treatment received within 60 days of MPS defined subgroups
Medical Therapy
n=9956


Early Revascularization
n=671
Primary Endpoint: Cardiac death, defined as death attributable to any
cardiovascular cause
Secondary Endpoint: All-cause mortality
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs Medical Therapy After Stress
SPECT: Primary Endpoint
Cardiac Death Rate per Treatment Group (%)
p=0.0004
4.0
2.8
%
3.0
2.0
1.3
1.0
0.0
Medical Therapy
Revascularization
• As a function of
treatment, medical
therapy and
revascularization
were associated with
1.3% and 2.8%
cardiac death rates,
respectively
(p=0.0004).
• During follow-up
there were 146
cardiac deaths (1.4%)
and 492 all-cause
mortality deaths
(4.6%).
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Cardiac Death Rate (%)
Revascularization vs Medical Therapy After Stress
SPECT: Total Myocardium Ischemia
• Observed (unadjusted)
mortality rates as a
Cardiac Death Rate per % of Total Myocardium function of the %
Ischemic (%)
myocardium ischemic
8.0
reveal that in the absence
6.7
of inducible ischemia,
6.3
patients treated medically
6.0
were at low risk; those
4.8
undergoing
revascularization were very
3.7
few in number and had a
4.0
3.3
single event, making the
2.9
interpretation of the event
2.0 rate limited.
1.8
2.0
• With increasing rates of
1.0
inducible ischemia,
0.7
mortality rates
n=7110 n=16 n=133 n=56 n=718 n=109 n=545 n=243 n=252 n=267
progressively increased in
0.0
1
patients undergoing
0%
1-5%
5-10%
11-20%
>20% medical therapy (p<0.0001)
Medical Treatment
Revascularization but not in patients referred
for revascularization.
Hachamovitch, et al., Circulation 2003; 107:2900-2906
Revascularization vs Medical Therapy After Stress
SPECT: Propensity Score
• To adjust for non-randomization of treatment, a
propensity score was developed using logistic
regression to model the decision to refer to
revascularization.
• This model (c index = 0.94, p<10-7) identified
inducible ischemia and anginal symptoms as the
most powerful predictors (83%, 6% of overall χ2) and
was incorporated into survival models.
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs. Medical Therapy After Stress
SPECT: Propensity Score (cont.)
• Increasing amounts
of inducible ischemia
were associated with
increasing likelihood
of revascularization,
with very sharp
increases between 0
to ~10% to 12.5%
myocardium
ischemic, with a
relative plateau in
this likelihood with
additional increases
in inducible ischemia.
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs. Medical Therapy After Stress
SPECT: Survival Analysis
• Based on the Cox proportional hazards model
predicting cardiac death, patients undergoing medical
therapy demonstrated a survival advantage over
patients undergoing revascularization in the setting of
no or mild ischemia, whereas patients undergoing
revascularization had an increasing survival benefit
over patients undergoing MT when moderate to severe
ischemia was present.
• Moreover, increasing survival benefit for
revascularization over medical therapy was noted in
higher risk patients (elderly, adenosine stress, and
women, especially those with diabetes).
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs. Medical Therapy After Stress
SPECT: Survival Analysis (cont.)
• These two lines
intersect at a value of
~10% to 12.5%
myocardium
ischemic, above
which the survival
benefit for
revascularization over
medical therapy
increases as a
function of increasing
amounts of inducible
ischemia.
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs. Medical Therapy After Stress
SPECT: Limitations
• Patients in observational studies better represent those
seen in practice and, unlike randomized clinical trials
(RCTs), can account for changes over time; however,
whether a survival benefit definitively exists at any level
of ischemia can only be answered by an RCT.
• It is unknown in how many patients revascularization
was not performed because of significant comorbidities
and it is possible that those with unmeasured
comorbidities were preferentially treated medically, thus
contributing to the early survival benefit found with
revascularization.
Hachamovitch, et al., Circulation 2003;
107:2900-2906
Revascularization vs. Medical Therapy After Stress
SPECT: Summary
• Compared with medical therapy,
revascularization had greater survival benefit,
both absolute and relative, in patients with
moderate to larger amounts of inducible
ischemia.
• If confirmed by prospective evaluations, these
findings will have significant consequences for
future approaches to post-single photon
emission computed tomography patient
management.
Hachamovitch, et al., Circulation 2003;
107:2900-2906