1. Published in Circulation 2003 Rory Hachamovitch, MD, MSc; Sean W. Hayes, MD; John D. Friedman, MD; Ishac Cohen PhD; Daniel S. Berman, MD 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

2. 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.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: Background

3.  Primary Endpoint: Cardiac death, defined as death attributable to any cardiovascular cause  Secondary Endpoint: All-cause mortality  Primary Endpoint: Cardiac death, defined as death attributable to any cardiovascular cause  Secondary Endpoint: All-cause mortality Medical Therapy n=9956 n=9956 Early Revascularization n=671 n=671 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 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 Hachamovitch, et al., Circulation 2003; 107:2900-2906 Revascularization vs Medical Therapy After Stress SPECT: Study Design

4. As a function of treatment, medical therapy and revascularization were associated with 1.3% and 2.8% cardiac death rates, respectively (p=0.0004).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%).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 per Treatment Group (%) % p=0.0004p=0.0004 Revascularization vs Medical Therapy After Stress SPECT: Primary Endpoint

5. Observed (unadjusted) mortality rates as a function of the % myocardium ischemic reveal that in the absence of inducible ischemia, patients treated medically were at low risk; those undergoing revascularization were very few in number and had a single event, making the interpretation of the event rate limited.Observed (unadjusted) mortality rates as a function of the % myocardium ischemic reveal that in the absence of inducible ischemia, patients treated medically were at low risk; those undergoing revascularization were very few in number and had a single event, making the interpretation of the event rate limited. With increasing rates of inducible ischemia, mortality rates progressively increased in patients undergoing medical therapy (p<0.0001) but not in patients referred for revascularization.With increasing rates of inducible ischemia, mortality rates progressively increased in patients undergoing medical therapy (p<0.0001) but not in patients referred for revascularization. Cardiac Death Rate (%) Cardiac Death Rate per % of Total Myocardium Ischemic (%) n=7110 n=16 Hachamovitch, et al., Circulation 2003; 107:2900-2906 n=267 n=252 n=243 n=545 n=109 n=718 n=56 n=133 1 Revascularization vs Medical Therapy After Stress SPECT: Total Myocardium Ischemia

6. To adjust for non-randomization of treatment, a propensity score was developed using logistic regression to model the decision to refer to revascularization.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 χ 2 ) and was incorporated into survival models.This model (c index = 0.94, p<10 -7 ) identified inducible ischemia and anginal symptoms as the most powerful predictors (83%, 6% of overall χ 2 ) and was incorporated into survival models. Hachamovitch, et al., Circulation 2003; 107:2900-2906 Revascularization vs Medical Therapy After Stress SPECT: Propensity Score

7. 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.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

8. 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.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).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

9. Revascularization vs. Medical Therapy After Stress SPECT: Survival Analysis (cont.) Hachamovitch, et al., Circulation 2003; 107:2900-2906 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.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.

10. 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.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.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. 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.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.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: Limitations

11. Compared with medical therapy, revascularization had greater survival benefit, both absolute and relative, in patients with moderate to larger amounts of inducible ischemia.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.If confirmed by prospective evaluations, these findings will have significant consequences for future approaches to post-single photon emission computed tomography patient management. Compared with medical therapy, revascularization had greater survival benefit, both absolute and relative, in patients with moderate to larger amounts of inducible ischemia.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.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 Revascularization vs. Medical Therapy After Stress SPECT: Summary